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  • CLASSES

    Psychostimulants, Amphetamines
    Stimulant Narcolepsy Agents

    BOXED WARNING

    Alcoholism, substance abuse

    Oral dextroamphetamine products are contraindicated in patients with a history of substance abuse; use transdermal dextroamphetamine with caution in these patients. Evaluate the child or adult patient for a history (or a family history of) abuse of prescription medicines or street drugs, or alcohol dependence or abuse (alcoholism). CNS stimulants, including dextroamphetamine and other amphetamine-containing products, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. Symptoms of chronic abuse include severe dermatoses, insomnia, irritability, hyperactivity, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders.

    DEA CLASS

    Rx, schedule II

    DESCRIPTION

    Oral and transdermal CNS stimulant; is the dextro-isomer of racemic amphetamine and twice as potent
    Used for treatment of attention-deficit hyperactivity disorder (ADD/ADHD) and narcolepsy in adult and pediatric patients; not suitable for chronic use for weight loss or weight management
    As with all CNS stimulants, there is a risk for abuse and dependence

    COMMON BRAND NAMES

    Dexedrine, Dexedrine Spansule, DextroStat, Liquadd, ProCentra, Zenzedi

    HOW SUPPLIED

    Dexedrine Spansule/Dextroamphetamine/Dextroamphetamine Sulfate Oral Cap ER: 5mg, 10mg, 15mg
    Dexedrine/Dextroamphetamine/Dextroamphetamine Sulfate/DextroStat/Zenzedi Oral Tab: 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg, 30mg
    Dextroamphetamine/Dextroamphetamine Sulfate/Liquadd/ProCentra Oral Sol: 5mg, 5mL

    DOSAGE & INDICATIONS

    For the treatment of attention-deficit hyperactivity disorder (ADHD).
    Oral dosage (tablets or solution, immediate-release)
    Adults

    Initially, 5 mg PO once daily or twice daily. If divided doses are required, give first dose upon awakening and the subsequent doses (1 or 2) at 4 to 6 hour intervals. Titrate by no more than 5 mg/day at weekly intervals to the minimum effective dose; doses greater than 40 mg/day are rarely needed. Max: 40 mg/day PO. Dosage should be individualized; use lowest effective dose after stabilization.

    Children and Adolescents 6 years and older

    Initially, 5 mg PO once or twice daily. May titrate daily dose in 5 mg increments at weekly intervals to minimum effective dose. Daily dose may be given in 1 to 3 divided doses at 4 to 6 hour intervals. Max: 40 mg/day PO. Doses greater than 40 mg/day are rarely needed, however, a maximum dose of 60 mg/day in patients weighing more than 50 kg may be considered.  Dosage should be individualized; use lowest effective dose after stabilization.

    Children 3 to 5 years

    Initially, 2.5 mg PO once daily in the morning. May titrate daily dose in 2.5 mg increments at weekly intervals to the minimum effective dose. Daily dose may be given in 1 to 3 divided doses at 4 to 6 hour intervals. Maximum dosage information is not available; however, dosage should not exceed 40 mg/day, the usual maximum recommended dose for children ages 6 to 12 years. Although this dosing information is available in the FDA-approved labeling, the American Academy of Pediatrics (AAP) does not recommend the use of dextroamphetamine in this age group due to lack of safety and efficacy data.

    Oral dosage (extended-release capsules)
    Adults†

    5 mg PO once or twice daily initially. Titrate by no more than 5 mg/day at weekly intervals to the minimum effective dose; doses greater than 40 mg/day are rarely needed. Max: 40 mg/day PO. Dosage should be individualized; use lowest effective dose after stabilization.

    Children and Adolescents 6 years and older

    Initially, 5 mg PO once or twice daily. May titrate by 5 mg increments at weekly intervals to a minimum effective dose. Twice daily dosing should be given with an interval of approximately 8 hours; avoid late evening administration. Max: 40 mg/day PO. Doses greater than 40 mg/day are rarely needed, however, a maximum dose of 60 mg/day in patients weighing more than 50 kg may be considered. Dosage should be individualized; use lowest effective dose after stabilization.

    Transdermal dosage (Xelstrym transdermal system)
    Adults

    One 9 mg/9 hours patch applied once daily in the morning every 24 hours, initially. Apply 2 hours before effect is needed and remove within 9 hours of application. May adjust up to a maximum of one 18 mg/9 hours patch per morning. Individualize dosage and titration based on response and tolerability. SWITCH FROM OTHER PRODUCTS: For patients switching from another medication or amphetamine product, discontinue current medication and start dextroamphetamine patch at one 9 mg/9 hours dose. Max: one 18 mg/9 hours patch per day.

    Children and Adolescents 6 years and older

    Initially, one 4.5 mg/9 hours patch applied once daily in the morning. Apply 2 hours before an effect is needed and remove within 9 hours of application. May adjust in weekly increments of 4.5 mg as needed/tolerated. Max: one 18 mg/9 hours patch applied daily. SWITCH FROM OTHER PRODUCTS: For patients switching from another medication or amphetamine product, discontinue current medication and start at 4.5 mg/9 hours dose.

    For the treatment of narcolepsy.
    Oral dosage (immediate-release tablets or solution)
    Adults, Adolescents, and Children 12 years and older

    Initially, 10 mg PO once daily in the morning. May titrate by 10 mg increments at weekly intervals to the minimum effective dose. Daily dose may be given in 1 to 3 divided doses at 4 to 6 hour intervals. Avoid late evening doses. Reduce dose if anorexia or insomnia occur. Usual dosage range: 5 to 60 mg/day PO, given in divided doses. Max: 60 mg/day PO.

    Children 6 to 11 years

    Initially, 5 mg PO once daily in the morning. May titrate by 5 mg increments at weekly intervals to the minimum effective dose. Daily dose may be given in 1 to 3 divided doses at 4 to 6 hour intervals. Although a specific maximum dose for children has not been identified, the usual maximum dose for narcolepsy is 60 mg/day. Reduce dose if anorexia or insomnia occur.

    Oral dosage (extended-release capsules)
    Adults, Adolescents, and Children 12 years and older

    Initially, 10 mg PO once daily in the morning. May increase dose by 10 mg at weekly intervals until an effective dose is achieved. Use lowest effective dose. The usual dosage range is 5 to 60 mg/day in divided doses; however, once daily administration may be appropriate for some patients. Twice daily dosing should be given with an interval of approximately 8 hours. Reduce dose if anorexia or insomnia occur. Max: 60 mg/day.

    Children 6 to 11 years

    Initially, 5 mg PO once daily in the morning. May increase by 5 mg increments at weekly intervals to minimum effective dose. Twice daily dosing should be given with an interval of approximately 8 hours. Reduce dose if anorexia or insomnia occur. Although a specific maximum has not been identified for this age group, the usual maximum dose for narcolepsy is 60 mg/day PO.

    For the short-term treatment (i.e., 3 to 6 weeks) of exogenous obesity† in adults.
    Oral dosage (tablets)
    Adults

    Use is not recommended; there are FDA-approved medication options that are recommended and preferred per obesity guidelines as adjuncts to lifestyle and exercise for selected patients. While amphetamine-related drugs have been used short-term for weight loss with success, the results are not sustained and they are not effective in long-term use. In one small study, a dose of 5 mg PO 3 times daily resulted in an average weight loss of 3 pounds over the 6-week study period. By the end of the third week, weight loss had plateaued. In a flexible-dose study of 15 to 30 mg/day PO in divided doses for 4 weeks, weight loss occurred at the rate of about 0.5 kg per week (approximately a 2 kg weight loss over 4 weeks). At the 6 month post-treatment follow-up, the weight loss had not been sustained.

    Oral dosage (extended-release capsule)
    Adults

    Use is not recommended; there are FDA-approved medication options that are recommended and preferred per obesity guidelines as adjuncts to lifestyle and exercise for selected patients. While amphetamine-related drugs have been used short-term for weight-loss with success, the results are not sustained and they are not effective in long-term use. In one small placebo-controlled clinical trial, 15 mg PO once daily of sustained-release dextroamphetamine resulted in an average weight loss of 1.2 pounds per week over a 6-week period. There were no data reported during the final post-drug week.

    For the treatment of hypothalamic obesity† after craniopharyngioma surgical resection.
    Oral dosage (immediate-release tablets or solution)
    Children and Adolescents 6 years and older

    Very limited data are available; further studies needed. 5 mg PO once daily in the morning, titrated by 2.5 mg increments in weekly intervals until a decrease in appetite, significant improvement in behavior, or an adverse reaction occurred was used in a small open-label study of 5 children (age 6 to 9.8 years) who failed traditional weight loss therapy (i.e., diet modification and behavior therapy). The mean maximum daily dosage was 16 +/- 2 mg, which was divided into 3 doses given before meals; dosage did not exceed 20 mg/day PO. Weight stabilization was attained within 1 month of therapy initiation and remained stable throughout the 24-month protocol. Mean body mass index (BMI) was 21 +/- 3.5 prior to surgery, 32 +/- 2.8 at the start of therapy, and 31 +/- 3.3 at the end of the 24-month protocol. Mean time from surgery to therapy initiation was 10 months (range: 9 to 14 months). Weight stabilization was contributed to increased activity vs. decreased caloric intake or insulin concentrations. Dextroamphetamine at a dose of 5 mg PO twice daily has been described in a retrospective review of 12 patients (age 12 to 21 years) of similar circumstance.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    40 mg/day PO for ADHD or 60 mg/day PO for narcolepsy; one 18 mg/9 hour transdermal patch applied per 24 hours for ADHD.

    Geriatric

    40 mg/day PO for ADHD or 60 mg/day PO for narcolepsy; one 18 mg/9 hour transdermal patch applied per 24 hours for ADHD.

    Adolescents

    40 mg/day PO for ADHD (doses up to 60 mg/day PO have been used off-label for weight more than 50 kg) or 60 mg/day PO for narcolepsy; one 18 mg/9 hour transdermal patch applied per 24 hours for ADHD.

    Children

    6 years and older: 40 mg/day PO for ADHD (doses up to 60 mg/day PO have been used off-label for weight more than 50 kg) or 60 mg/day PO for narcolepsy; one 18 mg/9 hour transdermal patch applied per 24 hours for ADHD.
    3 to 5 years: Maximum dosage information is not provided in the FDA-approved labeling; doses should not exceed 40 mg/day PO for immediate-release formulations. Do not use extended-release or transdermal formulations.
    Less than 3 years: Safety and efficacy have not been established.

    Infants

    Not indicated.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available. Hepatic dysfunction has the potential to inhibit the elimination of amphetamines and result in prolonged exposure; use with caution and titrate dosages carefully.

    Renal Impairment

    Oral dosage forms:
    Specific guidelines for dosage adjustments of oral dextroamphetamine in renal impairment are not available. Renal dysfunction has the potential to inhibit the elimination of amphetamines and result in prolonged exposure; use with caution and titrate dosages carefully.
     
    Transdermal system (Xelstrym):
    Severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2): Do not exceed one 13.5 mg/9 hour system applied once per 24 hours.
    End stage renal disease (eGFR less than 15 mL/minute/1.73 m2): Do not exceed one 9 mg/9 hour system applied once per 24 hours.
     
    Intermittent hemodialysis
    Dextroamphetamine is not dialyzable.

    ADMINISTRATION

    Oral Administration

    Administer the first dose of the day upon awakening. Subsequent doses during the day, if given, should be administered at least 6 hours before bedtime to avoid sleep interference. 

    Oral Solid Formulations

    Immediate-release tablets:
    Immediate-release dextroamphetamine tablets are typically administered in 1 to 3 daily doses; administer at 4 to 6 hour intervals.
     
    Extended-release capsules:
    Extended-release dextroamphetamine is typically administered in 1 to 2 daily doses; administer at approximately 8 hour intervals. Do not crush or chew.
    Dexedrine Spansule is a bead-filled capsule containing both immediate-release and delayed-release beads. If swallowing is difficult, the capsule may be opened and the entire contents gently sprinkled on a teaspoon of cool applesauce, yogurt, or other soft food and swallowed immediately (do not store for future use). The capsule contents (beads) should not be crushed or chewed. Follow with a drink of water or other liquid.

    Oral Liquid Formulations

    Oral solution:
    Administer oral solution using an oral calibrated measuring device.
    Immediate-release dextroamphetamine is typically administered in 1 to 3 daily doses; administer at 4 to 6 hour intervals.

    Topical Administration
    Transdermal Patch Formulations

    Xelstrym transdermal system:
    Patch should be applied 2 hours before the effect is needed and removed 9 hours after application.
    Do not cut or trim patch. Do not use if the patch is cut or damaged.
    Apply to intact, hairless or nearly hairless skin that has been cleaned with soap and water (not an alcohol-based product) and is dry and free of any powder, lotion, oil, or gel. Site of application can include chest, upper arm, upper back, flank, or hip. Do not apply patch to any other site. Avoid areas of tight clothing. Choose a new site each time a new patch is applied.
    Apply the patch immediately after removing it from the pouch. Gently peel away half of the clear plastic liner and apply the sticky side of the patch to the application site selected. Hold the edge of the remaining protective liner and peel it away from the patch. Avoid touching the adhesive side of the patch to avoid absorption of the medication. If adhesive is touched, wash hands with soap and water immediately. Do not use hand sanitizer in place of soap and water. Smooth the patch down and press firmly to ensure a secure application. Do not use dressings, tape or other adhesives on the patch.
    Throughout the day during the wear-time, check to ensure the patch is still smoothly adhered to the application site. If patch edges lift, smooth down and press firmly with the palm of the hand. Patch adherence may be affected by showering, bathing, swimming, or sweating.
    Parents or caregivers should instruct children wearing the patch to tell an adult if the patch becomes loose or falls off.
    Avoid exposing the patch to direct external heat sources (such as heating pads, hair dryers, electric blankets, or heated water beds) while wearing the patch. Direct heat may increase the rate and extent of absorption of the medication.
    If the patch falls off, do not reapply it. Dispose of the patch and apply a new one to a different application site. The total wear time for both the first patch and the replacement patch should not exceed 9 hours in a 24-hour period.
    After 9 hours of wearing, the patch may be removed, folded in half with sticky sides together, and disposed of. Remaining adhesive on the skin may be removed with oil-based products or soap and water.
    Disposal: After 9 hours of wearing, the patient or caregiver should remove the patch and fold in half so that adhesive sides stick to one another. Place the folded patch in a lidded container. Do NOT flush the patch down the toilet.

    STORAGE

    Dexedrine:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Dexedrine Spansule:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    DextroStat:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Liquadd :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    ProCentra :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Zenzedi:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Dextroamphetamine is contraindicated for use in patients with known hypersensitivity or idiosyncrasy to the sympathomimetic amines or any component of these products.

    Alcoholism, substance abuse

    Oral dextroamphetamine products are contraindicated in patients with a history of substance abuse; use transdermal dextroamphetamine with caution in these patients. Evaluate the child or adult patient for a history (or a family history of) abuse of prescription medicines or street drugs, or alcohol dependence or abuse (alcoholism). CNS stimulants, including dextroamphetamine and other amphetamine-containing products, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. Symptoms of chronic abuse include severe dermatoses, insomnia, irritability, hyperactivity, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders.

    Bipolar disorder, depression, mania, psychosis, schizophrenia, suicidal ideation

    Dextroamphetamine is contraindicated in patients in an agitated state. Stimulants such as dextroamphetamine should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur. An assessment should be performed prior to initiation of therapy to determine the risk for bipolar disorder in patients presenting with symptoms of depression. Due to its toxic effects in overdose, dextroamphetamine should only be used in those with major depression or suicidal ideation when absolutely necessary. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and postmarketing experience with ADHD medications. Although causality has not been established and these behaviors may be inherent to ADHD, close monitoring is recommended. Patients and their caregivers should be advised to promptly report any changes in mood or behavior. If suicide-related events emerge during treatment, consideration should be given to dose reduction or drug discontinuation, especially if symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. In psychotic individuals (e.g., schizophrenia), amphetamines may exacerbate behavioral disturbances, psychosis, or thought disorders.

    Hypertension, tachycardia

    Oral dextroamphetamine products are contraindicated in patients with moderate to severe hypertension or symptomatic cardiac disease; avoid dextroamphetamine transdermal system use in these patients also. Stimulant medications must be used very cautiously in patients with pre-existing hypertension, tachycardia, or other conditions in which a modest increase in blood pressure or heart rate could be detrimental. Stimulant medications cause a modest increase in average blood pressure (approximately 2 to 4 mmHg) and average heart rate (approximately 3 to 6 bpm); however, some individuals may have larger increases. Although these mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Elevated blood pressure may require a dose reduction, discontinuation, and/or initiation of appropriate antihypertensive medication.

    Acute myocardial infarction, aortic stenosis, arteriosclerosis, cardiac arrhythmias, cardiac disease, cardiomyopathy, congenital heart disease, coronary artery disease, heart failure, myocardial infarction, prosthetic heart valves, valvular heart disease, ventricular arrhythmias, ventricular dysfunction

    Oral dextroamphetamine products are contraindicated in patients with moderate to severe hypertension, advanced arteriosclerosis, or symptomatic cardiac disease; avoid dextroamphetamine transdermal system use in these patients also. Avoid dextroamphetamine use in patients with known serious structural cardiac abnormalities, aortic stenosis, prosthetic heart valves, valvular heart disease, coronary artery disease, cardiomyopathy, heart failure, serious cardiac arrhythmias or ventricular arrhythmias, ventricular dysfunction, or other serious cardiac problems. Sudden death and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Misuse of amphetamines may cause sudden death and serious cardiovascular events. Further evaluate patients who develop exertional chest pain, unexplained syncope, acute myocardial infarction, or arrhythmias during dextroamphetamine treatment. Conflicting data are available regarding the cardiovascular risk associated with stimulant use; it appears that the short-term risk of serious cardiac events is not significantly increased in otherwise healthy pediatric patients. The American Heart Association (AHA) states that it is reasonable to consider the use of medications for the treatment of ADHD in pediatric patients with congenital heart disease without current hemodynamic or arrhythmic concerns or congenital heart disease that is considered stable by the patient's pediatric cardiologist, unless the cardiologist has specific concerns. However, these patients should be closely monitored and treatment discontinuation should be considered if the patient develops any of the following conditions: heart condition associated with sudden cardiac death (SCD), arrhythmia requiring cardiopulmonary resuscitation, direct current cardioversion/defibrillation or overdrive pacing, arrhythmia associated with SCD, any clinically significant arrhythmia that is not treated or controlled, QTc on electrocardiogram (ECG) more than 0.46 seconds, or heart rate or blood pressure more than 2 standard deviations above the mean for age. All patients being considered for pharmacologic treatment of ADHD should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmia, and a physical exam to assess for the presence of cardiac disease. If cardiac disease is suspected, further cardiac evaluation including an ECG and echocardiogram is warranted. For pediatric patients, the AHA states that it may be useful to obtain a baseline ECG as a part of the initial evaluation. If a child or adolescent has any significant findings on physical examination, ECG, or family history, consult a pediatric cardiologist before initiating the medication.

    Cerebrovascular disease, stroke

    Stroke has occurred in adults receiving stimulants at usual doses for ADHD; therefore, patients with cerebrovascular disease should be closely monitored. Stimulant medications may increase blood pressure or heart rate in some individuals.

    Glaucoma, visual disturbance

    Oral dextroamphetamine products are contraindicated in patients with glaucoma, due to the ability of sympathetic stimulation to block aqueous outflow and raise intraocular pressure; use caution with dextroamphetamine transdermal. Occasionally, visual disturbance, such as blurred vision and accommodation, has been reported in individuals without ocular disease while they are taking dextroamphetamine. Patients should report any new visual disturbance as an ophthalmic evaluation may be needed.

    Hyperthyroidism, thyrotoxicosis

    Oral dextroamphetamine products, like other amphetamines, are contraindicated for use in thyroid disease patients with hyperthyroidism, including thyrotoxicosis, as sympathomimetic stimulation may induce cardiac arrhythmias or other side effects.

    Tics, Tourette's syndrome

    Amphetamines have been reported to exacerbate motor and phonic tics and Tourette's syndrome; evaluate for these prior to the use of stimulants, especially in pediatric patients. If stimulant therapy is warranted, administer under close supervision and at the lowest effective dose.

    Driving or operating machinery

    The use of amphetamine may cause dizziness, mask signs of fatigue or the need for rest, or impair the ability of a patient to participate in activities that require mental alertness. Patients should not perform such tasks, including driving or operating machinery, until they are aware of how this medication affects them.

    Radiographic contrast administration, seizure disorder, seizures

    Use dextroamphetamine with caution in patients with seizures or a history of a seizure disorder because the seizure threshold can be reduced, particularly during excess CNS stimulation (i.e., amphetamine overdosage). The effects of amphetamines on the seizure threshold, in normal therapeutic dosages, are less clear. Seizure threshold may be reduced in those with EEG abnormalities and rarely in patients without a seizure history or EEG abnormalities. If seizures occur, discontinuation of therapy is recommended. Because of a potential increased risk of seizures, amphetamines should not be used during intrathecal radiographic contrast administration. Amphetamines should be discontinued 48 hours before the myelography and should not be resumed until at least 24 hours after the procedure.

    Surgery

    The use of inhalational anesthetics during surgery may sensitize the myocardium to the effects of amphetamines and other sympathomimetic drugs. Patients should check with their surgeon prior to elective surgery regarding any adjustments needed in timing of medications for surgical procedures.

    Hepatic disease, renal impairment

    The elimination of amphetamine, including dextroamphetamine, is dependent on hepatic metabolism, urinary pH and urinary flow rates, as well as active secretion. Both hepatic disease and renal impairment have the potential to inhibit the elimination of amphetamines and result in prolonged exposures.

    Peripheral vascular disease, Raynaud's phenomenon

    Stimulant medications are associated with peripheral vasculopathy, including Raynaud's phenomenon. Worsening of peripheral vascular disease is possible. Effects on circulation have been observed with therapeutic doses at different times throughout therapy in all age groups. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor all patients for digital changes during treatment with stimulant medications, especially those with pre-existing circulation problems. Instruct patients to seek immediate medical attention if any new digital numbness, pain, skin discoloration, or temperature sensitivity occur, or if unexplained wounds appear on their fingers or toes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

    Heating pad

    Use of the dextroamphetamine patch does not need to be interrupted during bathing or hot weather, but prolonged exposure to an external heat source (such as a heating pad, hair dryer, hot tub, sauna, or electric blanket) should be avoided in order to avoid potential adverse effects from increased dextroamphetamine exposure. In clinical bioavailability studies of the dextroamphetamine patch, application of a heating pad for 6 consecutive hours increased both the rate and extent of dextroamphetamine absorption. Time to maximum concentration decreased to 6.5 hours with heat application (compared to 8.5 hours without), maximum concentration increased to 116%, and total exposure increased to 150% of dextroamphetamine concentrations seen without the use of an external heat source.

    Anorexia nervosa, bulimia nervosa, obesity treatment

    Eating disorders, such as anorexia nervosa or bulimia nervosa, should be ruled out prior to treatment with amphetamines. Patients with eating disorders may have physiologic complications, such as metabolic and electrolyte abnormalities, which may increase their susceptibility to the adverse effects of stimulants. The use of sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. The abuse potential of stimulants when used for weight loss should be considered. Dextroamphetamine products are not indicated or recommended for obesity treatment.

    Abrupt discontinuation

    Administration of amphetamines for a prolonged period of time may lead to physical and psychological drug dependence. Abrupt discontinuation after chronic use (therapeutic or recreational) may result in severe depressive symptoms, extreme fatigue, sleep EEG changes, and symptoms of withdrawal. Close supervision during gradual withdrawal of therapy is recommended.

    Geriatric

    Dextroamphetamine should be used with caution in the geriatric patient for the treatment of attention deficit/hyperactivity disorder (ADHD) or narcolepsy. Stimulant medications are used as the treatments of choice in the adult patient over 50 years of age with ADHD when behavioral and lifestyle modifications alone have failed to improve concerns associated with inattention, such as task focus and completion, or organization and time management. Medication should be initiated at low doses initially and titrated slowly to effect due to potential reductions in hepatic, renal, or cardiac function as well as concomitant medications or disease states. Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of the amphetamines; use with caution in the older adult. Side effects of amphetamines or other stimulants are usually mild but may include mood or behavior changes, tremor, insomnia, increased blood pressure, headache, or gastroesophageal reflux or other GI complaints. Adults should have their blood pressure and heart rate checked at baseline and periodically during treatment. If treatment is considered necessary, periodically re-evaluate the long-term usefulness of the drug for the individual patient.  

    Neonates, pregnancy

    There are no adequate and well-controlled studies of dextroamphetamine in pregnant women and dextroamphetamine should only be used during pregnancy if the expected benefit to the mother justifies the potential fetal risk. One case describes a neonate born with a severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia following maternal exposure to dextroamphetamine and lovastatin during the first trimester of pregnancy. Amphetamines have been shown to have both embryotoxic and teratogenic effects in some animals at doses higher than the maximum recommended human dose; however, most available data indicate that amphetamines are not teratogenic in humans. Among 671 mother-child pairs enrolled in the Collaborative Perinatal Project who had first trimester exposure to amphetamines and 1,898 mother-child pairs with amphetamine exposures at any time during pregnancy, there was no evidence suggesting a relationship to large categories of major or minor malformations. Non-teratogenic effects are known to occur in human neonates who are born to mothers dependent on amphetamines. These have included increased incidences of premature births, low birth weights and length, lower occipitofrontal circumference, and physical withdrawal symptoms (e.g., abnormal sleep patterns, dysphoria, poor feeding, tremor, agitation, fatigue, and hypertonia). In one prospective comparison study, neonates exposed to cocaine, methamphetamine, or a combination of cocaine and narcotic in utero had a 35.1% incidence of cranial abnormalities (i.e., intraventricular hemorrhage, echodensities known to be associated with necrosis, and cavitary lesions) compared to a 5.3% incidence in normal infants as assessed by cranial ultrasonography. The authors speculated that the ultrasonographic abnormalities were probably related to the vasoconstrictive properties of the drugs. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to dextroamphetamine; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1-866-961-2388.

    Breast-feeding

    Amphetamines are excreted into breast milk, and women who are taking amphetamines should be advised to refrain from breast-feeding. Long-term neurodevelopmental effects from amphetamine exposure via the breast milk are unknown. It is possible that large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in the nursing infant, including serious cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy, advise patients that breast-feeding is not recommended during treatment. Based on limited case reports in published literature, amphetamine (d- or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Methylphenidate may be considered an alternative, although the medical use of stimulant medications has not been formally evaluated during lactation. If breast-feeding cannot be avoided during administration of a stimulant, the nursing infant should be monitored for signs of central nervous system hyperactivity, including decreased appetite, insomnia, and irritability.

    Growth inhibition

    The potential for growth inhibition in pediatric patients should be monitored during stimulant therapy. Monitor height and weight parameters relative to age at treatment initiation and periodically thereafter (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. Data are inadequate to determine whether chronic use of stimulants, such as dextroamphetamine, causes long-term growth inhibition. Although data are limited, available studies do not indicate that stimulant use compromises the attainment of normal adult height and weight in most children. In a 24-month follow-up, the MultiModal Treatment Study showed a deceleration of growth of roughly 1 cm per year with stimulant use. In general, growth remained in the normal curve for most children, except those in the lowest percentiles of height for age. Data obtained on the effects of stimulants on growth suppression in children 7 to 10 years of age suggested that regularly medicated children (7 days/week throughout the year) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years. Reduction of annual growth rate was maximal in the first year, decreased in the second year, and absent in the third year of treatment; however, no compensatory growth rebound effects were found while on stimulant therapy. In a dose-optimization and crossover trial of transdermal dextroamphetamine use in patients 6 to 17 years old, mean weigh loss from baseline was -3.1 pounds after 5 weeks of use. Proposed mechanisms of growth inhibition include the suppression of appetite or an alteration in growth hormone secretion. Growth rebound has been observed after stimulant discontinuation and some experts recommend the use of drug holidays to allow growth to 'catch-up'. However, drug holidays are typically reserved for children with well-controlled attention-deficit hyperactivity disorder (ADHD) symptoms and are of unproved value in limiting growth suppression.

    MAOI therapy

    Dextroamphetamine is contraindicated in patients who are currently taking monoamine oxidase inhibitors (MAOIs) or have received MAOI therapy (including MAOIs such as linezolid or intravenous methylene blue) within the past 14 days because of an increased risk of hypertensive crisis. Clinicians should review drug-drug interactions. Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems, including the MAOIs. Discontinue treatment with any serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment.

    Laboratory test interference

    Amphetamines can cause a significant elevation in plasma corticosteroid levels; this increase is greatest in the evening. Amphetamines may cause laboratory test interference with urinary steroid determinations. These effects may need to be considered during testing.

    ADVERSE REACTIONS

    Severe

    bowel ischemia / Delayed / 0-1.0
    seizures / Delayed / 0.1-0.1
    Tourette's syndrome / Delayed / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    cardiac arrest / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    visual impairment / Early / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    stroke / Early / Incidence not known
    coma / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known

    Moderate

    constipation / Delayed / 1.0-10.0
    psychosis / Early / 0-0.2
    hallucinations / Early / 0.1-0.1
    mania / Early / 0.1-0.1
    supranormalization / Delayed / Incidence not known
    euphoria / Early / Incidence not known
    dyskinesia / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    hypertension / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    hostility / Early / Incidence not known
    priapism / Early / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    peripheral vasoconstriction / Rapid / Incidence not known
    blurred vision / Early / Incidence not known
    hyperreflexia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    hyperthermia / Delayed / Incidence not known
    delirium / Early / Incidence not known
    physiological dependence / Delayed / Incidence not known
    tolerance / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    psychological dependence / Delayed / Incidence not known

    Mild

    diarrhea / Early / 1.0-10.0
    headache / Early / 10.0
    abdominal pain / Early / 10.0
    emotional lability / Early / 10.0
    anorexia / Delayed / 10.0
    insomnia / Early / 10.0
    irritability / Delayed / 10.0
    xerostomia / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    nausea / Early / Incidence not known
    dyspepsia / Early / Incidence not known
    restlessness / Early / Incidence not known
    vomiting / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    tremor / Early / Incidence not known
    syncope / Early / Incidence not known
    dizziness / Early / Incidence not known
    agitation / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    libido increase / Delayed / Incidence not known
    rash / Early / Incidence not known
    vesicular rash / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    mydriasis / Early / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Acebutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Codeine: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Acetaminophen; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Acetaminophen; Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, 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.
    Acetazolamide: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Aclidinium; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant atomoxetine and formoterol use. Concomitant use may potentiate sympathetic effects.
    Albiglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Albuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and amphetamine; dextroamphetamine use. Concomitant use may potentiate sympathetic effects.
    Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aliskiren; Amlodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Aliskiren; Valsartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Alkalinizing Agents: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Alogliptin; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Alpha-glucosidase Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Aluminum Hydroxide: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Aluminum Hydroxide; Magnesium Carbonate: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Aluminum Hydroxide; Magnesium Hydroxide: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Aluminum Hydroxide; Magnesium Trisilicate: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Amantadine: (Moderate) Careful observation is required when amantadine is administered concurrently with central nervous system (CNS) stimulants. An increase in stimulant effects, such as nervousness, irritability, insomnia, tremor, seizures, or cardiac arrhythmias may occur.
    Ambrisentan: (Minor) Sympathomimetics such as amphetamine or dextroamphetamine can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy of ambrisentan.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with amphetamines and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Amphetamines may increase the risk of seizures.
    Amiloride; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Amlodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Atorvastatin: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Benazepril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Celecoxib: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Olmesartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Amlodipine; Valsartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Ammonium Chloride: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Amoxapine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of indirect-acting sympathomimetics, such as amphetamine, however, the data are not consistent.
    Angiotensin II receptor antagonists: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Angiotensin-converting enzyme inhibitors: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Antacids: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Arformoterol: (Moderate) Caution and close observation should be used when arformoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Armodafinil: (Moderate) The use of armodafinil with other psychostimulants, including amphetamines, (e.g., dextroamphetamine, lisdexamfetamine, amphetamine) has not been studied. In a single-dose study of dextroamphetamine combined with modafinil, a racemic compound containing armodafinil, no pharmacokinetic interactions occurred but a slight increase in stimulant-associated side effects was noted. Patients receiving combination therapy of armodafinil with other psychostimulants should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related side effects.
    Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
    Ascorbic Acid, Vitamin C: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Aspirin, ASA; Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Aspirin, ASA; Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, 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.
    Atenolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Atenolol; Chlorthalidone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Atomoxetine: (Moderate) Monitor blood pressure during concomitant amphetamine; dextroamphetamine and atomoxetine use. Because of possible effects on blood pressure. atomoxetine should be used cautiously with other drugs that affect blood pressure, such as amphetamine; dextroamphetamine.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Azilsartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Azilsartan; Chlorthalidone: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Benazepril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Benazepril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Bendroflumethiazide; Nadolol: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Beta-blockers: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Betaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
    Bisoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Bretylium: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
    Brimonidine; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Bromocriptine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Budesonide; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant atomoxetine and formoterol use. Concomitant use may potentiate sympathetic effects.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant atomoxetine and formoterol use. Concomitant use may potentiate sympathetic effects.
    Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
    Buprenorphine: (Moderate) If concomitant use of buprenorphine and amphetamines is warranted, 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.
    Buprenorphine; Naloxone: (Moderate) If concomitant use of buprenorphine and amphetamines is warranted, 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.
    Bupropion: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including amphetamine; dextroamphetamine. Use low initial doses of bupropion and increase the dose gradually.
    Bupropion; Naltrexone: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including amphetamine; dextroamphetamine. Use low initial doses of bupropion and increase the dose gradually.
    Buspirone: (Moderate) Coadministration of buspirone with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Buspirone has some serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Caffeine; Sodium Benzoate: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Calcium Carbonate: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions. (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Calcium Carbonate; Magnesium Hydroxide: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Calcium Carbonate; Risedronate: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Calcium Carbonate; Simethicone: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
    Calcium; Vitamin D: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Calcium-channel blockers: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Canagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Canagliflozin; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Candesartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Candesartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Captopril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Captopril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Carteolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Carvedilol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Celecoxib; Tramadol: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as tramadol. 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. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and tramadol. Patients receiving tramadol and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and tramadol should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, the risk of seizures from the use of tramadol may be increased with concomitant use of CNS stimulants that may induce seizures, including the amphetamines. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Chlorothiazide: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Chlorpheniramine; Codeine: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Chlorpheniramine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Chlorthalidone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Chlorthalidone; Clonidine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents
    Cimetidine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
    Cinacalcet: (Moderate) Warn patients that there are potentially serious drug interactions between cinacalcet and prescription amphetamine therapy or illicit amphetamine use. The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as cinacalcet. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Citalopram: (Moderate) Coadministration of selective serotonin reuptake inhibitors (SSRIs) like citalopram with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Clevidipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Clonidine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents
    Cocaine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
    Codeine: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Codeine; Guaifenesin: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Codeine; Phenylephrine; Promethazine: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Codeine; Promethazine: (Moderate) If concomitant use of codeine and amphetamines is warranted, 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.
    Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Dacomitinib: (Moderate) Warn patients that the risk of amphetamine toxicity, including serotonin syndrome, may be increased during concurrent use with dacomitinib. Concurrent use of dacomitinib, a strong CYP2D6 inhibitor, may increase exposure to the amphetamine increasing the risk for serotonin syndrome. If serotonin syndrome occurs, both the amphetamine and dacomitinib should be discontinued and appropriate medical treatment should be implemented.
    Dapagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Delavirdine: (Moderate) Warn patients that there are potentially serious drug interactions between delavirdine and prescription amphetamine therapy or illicit amphetamine use. The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as delavirdine. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Desvenlafaxine: (Moderate) Coadministration of amphetamines with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Dextromethorphan; Quinidine: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of quinidine, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Dihydroergotamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Diltiazem: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Dorzolamide; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Doxazosin: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving doxazosin and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as doxazosin.
    Dronabinol: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
    Dulaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Duloxetine: (Moderate) Coadministration of amphetamines with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Dyphylline: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
    Dyphylline; Guaifenesin: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
    Empagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Enalapril, Enalaprilat: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Enalapril; Felodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Enflurane: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
    Eplerenone: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving eplerenone and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
    Epoprostenol: (Major) Avoid use of sympathomimetic agents with epoprostenol. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including epoprostenol. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Eprosartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Ergoloid Mesylates: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ergonovine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ergot alkaloids: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ergotamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ergotamine; Caffeine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Ertugliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Ertugliflozin; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Escitalopram: (Moderate) Coadministration of selective serotonin reuptake inhibitors (SSRIs) like escitalopram with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Esketamine: (Major) Closely monitor blood pressure during concomitant use of esketamine and an amphetamine. Coadministration of psychostimulants, such as amphetamines, with esketamine may increase blood pressure, including the possibility of hypertensive crisis.
    Eslicarbazepine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Esmolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Ethanol: (Major) Advise patients to avoid alcohol while taking some dosage forms (e.g., Mydayis extended-release capsules) of amphetamine/dextroamphetamine salts. Consumption of alcohol while taking such dosage forms may result in a more rapid release of the dose of mixed amphetamine salts. Such effects may potentially lead to serious side effects such as acute anxiety, problems with sleep, or increases in heart rate or blood pressure that may lead to heart problems or stroke. (Major) Alcohol should not be consumerd with some dosage forms (e.g., Mydayis extended-release capsules) of amphetamine/dextroamphetamine salts. Consumption of alcohol while taking such dosage forms may result in a more rapid release of the dose of mixed amphetamine salts. Such effects may potentially lead to serious side effects such as acute anxiety, problems with sleep, or increases in heart rate or blood pressure that may lead to heart problems or stroke.Also, the use of amphetamine/dextroamphetamine salts may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicles; the patient should therefore be cautioned accordingly.
    Etomidate: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Exenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Famotidine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
    Felodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Fenfluramine: (Moderate) Use fenfluramine and amphetamines with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fentanyl: (Moderate) If concomitant use of fentanyl and amphetamines is warranted, 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.
    Fluoxetine: (Moderate) Coadministration of fluoxetine and amphetamines may increase the risk for serotonin syndrome or amphetamine-related side effects. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after initiation of therapy, dose increases, or the addition of other serotonergic medications. Discontinue serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. In addition, amphetamines are partially metabolized by CYP2D6 and fluoxetine is a strong CYP2D6 inhibitor. Increased systemic exposure to amphetamines from CYP2D6 inhibition may cause increased blood pressure or heart rate, anxiety, insomnia, or other amphetamine-related adverse effects.
    Fluticasone; Salmeterol: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and salmeterol use. Concomitant use may potentiate sympathetic effects.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Fluticasone; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Fluvoxamine: (Moderate) Coadministration of selective serotonin reuptake inhibitors (SSRIs) like fluvoxamine with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Food: (Moderate) In general, food does not significantly interact with the amphetamine stimulants, a dose may be taken with or without food. However, certain gastrointestinal acidifying agents (e.g., certain fruit juices, etc.) can lower the oral absorption of amphetamines. To ensure proper absorption, it may be prudent for the patient to avoid citrus fruits and citrus juices 1 hour before a dose, at the time of dosing, and for the 1 hour following a dose. In addition, the excretion of amphetamines is increased in acidic urine and decreased in alkaline urine. Foods that acidify the urine, such as cranberry juice, orange juice, or those that contain vitamin C (ascorbic acid) may increase amphetamine renal excretion. Conversely, foods that alkalinize the urine, such as beets, dairy products, kale, spinach may slightly slow urinary excretion of amphetamines. Patients should not significantly alter their diets, however, as these changes in urinary pH from foods are not expected to be clinically significant for most patients. (Minor) In general, food does not significantly interact with the amphetamine stimulants, a dose may be taken with or without food. Foods that alkalinize the urine, such as beets, dairy products, kale, spinach may slightly slow urinary excretion of amphetamines. Patients should not significantly alter their diets, however, as these alkaline changes in urinary pH from foods are not expected to be clinically significant for most patients.
    Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant atomoxetine and formoterol use. Concomitant use may potentiate sympathetic effects.
    Formoterol; Mometasone: (Moderate) Monitor blood pressure and heart rate during concomitant atomoxetine and formoterol use. Concomitant use may potentiate sympathetic effects.
    Fosinopril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Glimepiride; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glipizide; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Glyburide; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Glycopyrrolate; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant atomoxetine and formoterol use. Concomitant use may potentiate sympathetic effects.
    Green Tea: (Major) Some green tea products contain caffeine. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously.
    Guaifenesin; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Guanabenz: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of guanabenz when administered concomitantly. Patients should be monitored for loss of blood pressure control.
    Guanfacine: (Moderate) Sympathomimetic agents, such as amphetamines, may increase blood pressure and reduce the antihypertensive effects of antihypertensive agents, such as guanfacine. Monitor blood pressure and heart rate periodically when prescribed together. Guanfacine may be used adjunctively to psychostimulants such as amphetamines in the treatment of attention deficit hyperactivity disorder (ADHD). Pharmacokinetic studies reveal that guanfacine does not influence lisdexamfetamine pharmacokinetics and lisdexamfetamine does not affect guanfacine pharmacokinetics. No dosage adjustments are required when guanfacine and amphetamines are used together for ADHD. Monitor heart rate, blood pressure and for sedation during ADHD treatment.
    H2-blockers: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
    Homatropine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving methyldopa and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents
    Hydrochlorothiazide, HCTZ; Moexipril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Hydrocodone; Ibuprofen: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Hydrocodone; Phenylephrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, 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.
    Hydromorphone: (Moderate) If concomitant use of hydromorphone and amphetamines is warranted, 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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Ibritumomab Tiuxetan: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Ibuprofen; Famotidine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
    Ibuprofen; Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, 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.
    Iloprost: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Incretin Mimetics: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indapamide: (Moderate) Indapamide may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics and related drugs like indapamide may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate.
    Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulins: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Ipratropium; Albuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and amphetamine; dextroamphetamine use. Concomitant use may potentiate sympathetic effects.
    Irbesartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Isocarboxazid: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Isoflurane: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Isradipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Ketamine: (Moderate) Closely monitor vital signs when ketamine and amphetamine; dextroamphetamine salts are coadministered; consider dose adjustment individualized to the patient's clinical situation. Amphetamine; dextroamphetamine salts may enhance the sympathomimetic effects of ketamine.
    Labetalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. 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 all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Levalbuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and amphetamine; dextroamphetamine use. Concomitant use may potentiate sympathetic effects.
    Levamlodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Levobetaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Levobunolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Levomilnacipran: (Moderate) Coadministration of amphetamines with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Levorphanol: (Moderate) If concomitant use of levorphanol and amphetamines is warranted, 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.
    Levothyroxine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
    Linagliptin; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Linezolid: (Contraindicated) Amphetamines should not be administered during or within 14 days after the use of linezolid. Linezolid possesses MAO-inhibiting activity and can prolong and intensify the cardiac stimulation and vasopressor effects of the amphetamines, potentially resulting in hypertensive crisis. Linezolid also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. If serotonin syndrome occurs, discontinue serotonergic drugs and institute appropriate medical management.
    Liothyronine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Lisinopril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Lithium: (Moderate) Coadministration of amphetamines and lithium may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Lithium has central serotonergic effects. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation, after a dose increase, or the addition of other serotonergic medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Loop diuretics: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Lopinavir; Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Lorcaserin: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and lorcaserin. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. 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 all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. Also, the safety and efficacy of coadministration of lorcaserin with other products for weight loss, including amphetamines, have not been established.
    Losartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Losartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Loxapine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Lurasidone: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Magnesium Hydroxide: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
    Maprotiline: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
    Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Meperidine: (Moderate) If concomitant use of meperidine and amphetamines is warranted, 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.
    Meperidine; Promethazine: (Moderate) If concomitant use of meperidine and amphetamines is warranted, 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.
    Metaproterenol: (Major) Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Metformin; Repaglinide: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Metformin; Rosiglitazone: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Saxagliptin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Metformin; Sitagliptin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells.
    Methadone: (Moderate) If concomitant use of methadone and amphetamines is warranted, 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.
    Methazolamide: (Moderate) Urinary alkalinizers, such as methazolamide, result in decreased renal excretion of amphetamines. Monitor for amphetamine-related side effects. Avoid concomitant use in amphetamine overdose situations.
    Methenamine: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methenamine; Sodium Acid Phosphate: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Contraindicated) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methenamine; Sodium Salicylate: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methohexital: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Methyclothiazide: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Methyldopa: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving methyldopa and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents
    Methylene Blue: (Contraindicated) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma.
    Methylergonovine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Methysergide: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Metolazone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Metoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Miglitol: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Milnacipran: (Moderate) Coadministration of amphetamines with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Mirtazapine: (Moderate) Coadministration of mirtazapine with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Modafinil: (Moderate) The use of modafinil with other psychostimulants, including amphetamines (e.g., amphetamine, dextroamphetamine. lisdexamfetamine), has not been extensively studied. Patients receiving combination therapy of modafinil with other psychostimulants should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other CNS stimulant-related side effects. In single-dose studies of dextroamphetamine combined with modafinil, no significant pharmacokinetic interactions occurred, but a slight increase in stimulant-associated side effects was noted.
    Moexipril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Molindone: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Monoamine oxidase inhibitors: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Morphine: (Moderate) If concomitant use of morphine and amphetamines is warranted, 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.
    Morphine; Naltrexone: (Moderate) If concomitant use of morphine and amphetamines is warranted, 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.
    Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
    Nadolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Nalbuphine: (Moderate) If concomitant use of nalbuphine and amphetamines is warranted, 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.
    Nebivolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Nebivolol; Valsartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Nefazodone: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and nefazodone. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. 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 all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Nicardipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Nifedipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Nimodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Nirmatrelvir; Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Nisoldipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Nitrates: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
    Nizatidine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
    Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amphetamines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Olanzapine; Fluoxetine: (Moderate) Coadministration of fluoxetine and amphetamines may increase the risk for serotonin syndrome or amphetamine-related side effects. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after initiation of therapy, dose increases, or the addition of other serotonergic medications. Discontinue serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. In addition, amphetamines are partially metabolized by CYP2D6 and fluoxetine is a strong CYP2D6 inhibitor. Increased systemic exposure to amphetamines from CYP2D6 inhibition may cause increased blood pressure or heart rate, anxiety, insomnia, or other amphetamine-related adverse effects.
    Oliceridine: (Moderate) If concomitant use of oliceridine and amphetamines is warranted, 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.
    Olmesartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Omeprazole; Sodium Bicarbonate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, 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.
    Oxymorphone: (Moderate) If concomitant use of oxymorphone and amphetamines is warranted, 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.
    Ozanimod: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
    Paroxetine: (Moderate) Coadministration of paroxetine and amphetamines may increase the risk for serotonin syndrome or amphetamine-related side effects. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after initiation of therapy, dose increases, or the addition of other serotonergic medications. Discontinue serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. In addition, amphetamines are partially metabolized by CYP2D6 and paroxetine is a strong CYP2D6 inhibitor. Increased systemic exposure to amphetamines from CYP2D6 inhibition may cause increased blood pressure or heart rate, anxiety, insomnia, or other amphetamine-related adverse effects.
    Penbutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Pergolide: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Perindopril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Perindopril; Amlodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Phenelzine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Phenobarbital: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Phenoxybenzamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Phentermine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established.
    Phentermine; Topiramate: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. (Moderate) Monitor for amphetamine-related adverse events if coadministered with topiramate. Concurrent use may increase amphetamine concentrations, resulting in potentiation of the action of amphetamines.
    Phentolamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Phenytoin: (Moderate) Monitor for decreased efficacy of phenytoin during coadministration with amphetamine; dextroamphetamine salts. Amphetamines may delay the intestinal absorption of phenytoin.
    Pindolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Pioglitazone; Glimepiride: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Pioglitazone; Metformin: (Moderate) Monitor for loss of glycemic control when amphetamines are administered to patients taking antidiabetic agents. Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Sympathomimetic agents, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Pirbuterol: (Moderate) Caution and close observation should also be used when pirbuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Potassium Bicarbonate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Potassium Citrate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Potassium Citrate; Citric Acid: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Potassium-sparing diuretics: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Pramlintide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Prazosin: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving prazosin and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as prazosin.
    Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. Amphetamines may potentiate the pressor effects of epinephrine.
    Primidone: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Probenecid; Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Propofol: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Propranolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Proton pump inhibitors: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
    Quinapril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Quinapril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Quinidine: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of quinidine, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using racepinephrine inhalation are advised to avoid other non-prescription products containing sympathomimetics since additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate or blood pressure may be additive. Patients should avoid use of non-prescription decongestants, such as phenylephrine and pseudoephedrine, while using racepinephrine inhalations. Patients should avoid dietary supplements containing ingredients that are reported or claimed to have a stimulant or weight-loss effect, such as ephedrine and ephedra, Ma huang, and phenylpropanolamine. Patients taking prescription sympathomimetic or stimulant medications (including amphetamines, methylphenidate, dexmethylphenidate, isometheptane, epinephrine) should seek health care professional advice prior to the use of racepinephrine inhalations; consider therapeutic alternatives to racepinephrine for these patients.
    Ramipril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Ranitidine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
    Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.
    Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Reserpine: (Major) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as reserpine, lowers the absorption of amphetamines, reducing their efficacy. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure such as reserpine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Sacubitril; Valsartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Safinamide: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
    Salmeterol: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and salmeterol use. Concomitant use may potentiate sympathetic effects.
    Sedating H1-blockers: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
    Selegiline: (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.
    Selexipag: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Semaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Serotonin norepinephrine reuptake inhibitors: (Moderate) Coadministration of amphetamines with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Serotonin-Receptor Agonists: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Although unlikely to occur during monotherapy with serotonin-receptor agonists (or "triptans"), serotonin syndrome may occur from combining these drugs with other medications that potentiate serotonin activity. 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 all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Sertraline: (Moderate) Coadministration of selective serotonin reuptake inhibitors (SSRIs) like sertraline with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Sevoflurane: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    SGLT2 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Sibutramine: (Contraindicated) Sibutramine is contraindicated in patients taking other centrally-acting appetite suppressant drugs (e.g., amphetamines). Consider alternatives. Concurrent use of sibutramine with amphetamines can raise blood pressure and heart rate. Use of sibutramine with other serotonergic agents, such as the amphetamines, also increases the risk for serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Discontinue treatment with the amphetamine and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment.
    Sodium Acetate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Sodium Bicarbonate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Sodium Citrate; Citric Acid: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Sodium Lactate: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Sodium Oxybate: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
    Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and amphetamines, which are CNS stimulants. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
    Sotalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    St. John's Wort, Hypericum perforatum: (Moderate) Coadministration of St. John's Wort with amphetamines may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Succinimides: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. The amphetamines may also delay the intestinal absorption of ethosuximide; the extent of absorption of these seizure medications is not known to be affected.
    Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Sulfonylureas: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Tapentadol: (Moderate) If concomitant use of tapentadol and amphetamines is warranted, 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.
    Tedizolid: (Minor) Theoretically, drugs that possess MAO-inhibiting activity, such as tedizolid, can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid, which is structurally similar to tedizolid, and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including amphetamines.
    Telmisartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Telmisartan; Amlodipine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Terazosin: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving terazosin and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as terazosin.
    Terbutaline: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. Seizures or cardiac arrhythmias are also possible. (Moderate) Concurrent administration of theophylline or aminophylline with sympathomimetics can produce excessive stimulation manifested by skeletal muscle activity, agitation, and hyperactivity.
    Thiazide diuretics: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Thiazolidinediones: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Thiopental: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Thiothixene: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Thyroid hormones: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Tipranavir: (Moderate) Warn patients that there are potentially serious drug interactions between tipranavir and prescription amphetamine therapy or illicit amphetamine use. The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as tipranavir. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, discontinue both the amphetamine and CYP2D6 inhibitor and initiate appropriate medical treatment.
    Tirzepatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Topiramate: (Moderate) Monitor for amphetamine-related adverse events if coadministered with topiramate. Concurrent use may increase amphetamine concentrations, resulting in potentiation of the action of amphetamines.
    Tramadol: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as tramadol. 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. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and tramadol. Patients receiving tramadol and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and tramadol should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, the risk of seizures from the use of tramadol may be increased with concomitant use of CNS stimulants that may induce seizures, including the amphetamines. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Tramadol; Acetaminophen: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as tramadol. 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. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and tramadol. Patients receiving tramadol and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and tramadol should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, the risk of seizures from the use of tramadol may be increased with concomitant use of CNS stimulants that may induce seizures, including the amphetamines. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Trandolapril: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Trandolapril; Verapamil: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Tranylcypromine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Trazodone: (Moderate) Coadministration of trazodone and amphetamines may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. The MAOI activity of amphetamines may also be of concern with trazodone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Triamterene; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Tricyclic antidepressants: (Moderate) Use of amphetamines with tricyclic antidepressants may increase the risk for serotonin syndrome or have effects on blood pressure or heart rate. Monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. Also monitor blood pressure and heart rate. If the patient experiences changes in heart rate or rhythm, an ECG may be indicated. A dose reduction of one or both agents may be needed if side effects occur.
    Tromethamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
    Tryptophan, 5-Hydroxytryptophan: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as tryptophan. 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. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and tryptophan. Patients receiving tryptophan and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and tryptophan should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Valsartan: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Vasodilators: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
    Venlafaxine: (Moderate) Coadministration of amphetamines with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Verapamil: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Vilazodone: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and vilazodone. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of amphetamines and vonoprazan. Vonoprazan reduces intragastric acidity, which may increase the exposure of amphetamines and risk of toxicity.
    Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of amphetamines and vonoprazan. Vonoprazan reduces intragastric acidity, which may increase the exposure of amphetamines and risk of toxicity.
    Vortioxetine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and vortioxetine. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Ziprasidone: (Minor) Serotonin syndrome has been reported during the combined use of amphetamine stimulants and other medications with serotonergic properties. Serotonin syndrome has been reported during postmarketing use of ziprasidone; however, a causal relationship has not been established.
    Zonisamide: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.

    PREGNANCY AND LACTATION

    Pregnancy

    Amphetamines are excreted into breast milk, and women who are taking amphetamines should be advised to refrain from breast-feeding. Long-term neurodevelopmental effects from amphetamine exposure via the breast milk are unknown. It is possible that large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in the nursing infant, including serious cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy, advise patients that breast-feeding is not recommended during treatment. Based on limited case reports in published literature, amphetamine (d- or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Methylphenidate may be considered an alternative, although the medical use of stimulant medications has not been formally evaluated during lactation. If breast-feeding cannot be avoided during administration of a stimulant, the nursing infant should be monitored for signs of central nervous system hyperactivity, including decreased appetite, insomnia, and irritability.

    MECHANISM OF ACTION

    Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity.
    Actions in ADHD: The exact mode of therapeutic action in ADHD is not known. There is no conclusive evidence for the mechanism(s) of action of amphetamines on the mental and behavioral conditions in ADHD. Improved attention spans, decreased distractability, increased ability to follow directions or complete tasks, and decreased impulsivity and aggression have been noted when stimulants are prescribed for the treatment of ADHD. Data suggest that the modulation of serotonergic pathways by the amphetamines may contribute to the calming effects in the treatment of this disorder.
    Peripheral actions: Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. In the periphery, the actions of amphetamines are believed to occur through release of norepinephrine from the adrenergic nerve terminals and by a direct stimulant action on alpha- and beta-receptors. Heart rate typically increases slightly with normal therapeutic doses of stimulants (about 3 to 6 bpm); however, a reflexive decrease in heart rate in response to increased blood pressure can also occur. At high doses, such as in overdoses, amphetamine and its derivatives can cause significant hypertension, tachycardia, arrhythmias, and other serious complications. Amphetamines have some anorexic properties in short-term use, but they are not effective for long-term weight management.

    PHARMACOKINETICS

    Dextroamphetamine is administered orally or transdermally. Distribution is to most body tissues with high concentrations found in the CNS. Metabolism occurs in the liver and excretion is via the kidney. Under normal physiologic conditions the plasma half-life is 10 to 12 hours in adults following oral administration. When the transdermal system is removed after 9 hours wear time, the mean apparent elimination half-life of dextroamphetamine ranged from 6.4 to 11.5 hours in the pediatric and adult population, respectively.The urinary elimination of amphetamines may be affected by agents that acidify or alkalinize the urinary fluids. In general, for every 1 unit increase in urinary pH, there is a reported 7-hour increase in amphetamine half-life. Conversely, acidification of the urine speeds amphetamine elimination.]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6
    The specific enzymes involved in amphetamine metabolism have not been described; however, the formation of 4-hydroxy-amphetamine is known to involve CYP2D6. Since CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a possibility. The concomitant use of dextroamphetamine and CYP2D6 inhibitors may increase the exposure of dextroamphetamine compared to the use of the drug alone. Amphetamines are not an in vitro inhibitor of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A, nor an in vitro inducer of CYP1A2, CYP2B6, or CYP3A4/5. Amphetamines are not an in vitro substrate for P-glycoprotein (P-gp).

    Oral Route

    Dextroamphetamine is readily absorbed from the GI tract following oral administration. After administration of two 5 mg regular-release tablets to healthy volunteers, peak blood concentrations of 29.2 ng/mL were achieved at 2 hours post-dose. Administration of 10 mg of oral solution produced an average peak blood level of 33.2 ng/mL. Following administration of a 15 mg extended-release capsule, peak blood concentrations were achieved within an average of 8 to 10 hours post-dose. However, the onset of action occurs before peak serum concentrations are reached; onset of action is typically within 1 hour of dosage administration. Following administration of the oral solution, an average of 38% of the dose was recovered in the urine in 48 hours.

    Topical Route

    Transdermal system (Xelstrym): After a single 9-hour transdermal system patch application in pediatric patients 6 to 12 years with ADHD, the max concentration and AUC of dextroamphetamine were dose-proportional over the dose range of 4.5 mg/9 hours to 18 mg/9 hours. Peak plasma levels of dextroamphetamine were typically reached at 6 to 9 hours after single application and 6 hours after repeat applications. After repeat applications of the patch for 4 weeks in adults with ADHD, there was a 46% increase in max concentration and an 54% increase in AUC when rotating application sites for each application. There was an 86% increase in max concentration and 104% increase in AUC when applied to the same site over the 4-week period. When removed after 9 hours of wear time, the elimination half-life of dextroamphetamine ranged from 6.4 to 11.5 hours in the pediatric and adult population, respectively. In clinical bioavailability studies of the dextroamphetamine patch, application of a heating pad for 6 consecutive hours increased both the rate and extent of dextroamphetamine absorption. Time to maximum concentration decreased to 6.5 hours with heat application (compared to 8.5 hours without), maximum concentration increased to 116%, and total exposure increased to 150% of dextroamphetamine concentrations seen without the use of an external heat source.