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    Psychostimulants, Amphetamines

    BOXED WARNING

    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 ...

    Amphetamine; dextroamphetamine is contraindicated in patients with symptomatic cardiac disease, advanced arteriosclerosis, and moderate to severe hypertension. The FDA recommends that, in general, stimulant medications not be used in patients with known serious cardiac structural abnormalities, a history of acute myocardial infarction, aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, ventricular dysfunction or heart failure, cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. Stimulant medications may increase blood pressure or heart rate in some individuals; more serious cardiac effects have also been associated with stimulant use. Sudden unexplained death (SUD) and myocardial infarction have occurred in adults receiving stimulants at standard dosages for attention-deficit hyperactivity-disorder (ADHD). Sudden death has also been associated with stimulant medications at usual doses in pediatrics with structural cardiac abnormalities or other serious heart problems. A large retrospective cohort study including over 1.2 million children and young adults 2—24 years of age did not find an increased risk of serious cardiovascular events in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiovascular disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The American Heart Association (AHA) states that it is reasonable to consider the use of these medications 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) > 0.46 sec, or heart rate or blood pressure > 2 SD above the mean for age. All patients being considered for treatment with stimulant medications should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmias, 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 is reasonable 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 stimulant medication. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history.

    DEA CLASS

    Rx, schedule II

    DESCRIPTION

    Central nervous system (CNS) stimulant
    Used for attention-deficit hyperactivity disorder (ADHD) and narcolepsy
    Amphetamine and dextroamphetamine mixed salts allow for once-daily dosing

    COMMON BRAND NAMES

    Adderall, Adderall XR

    HOW SUPPLIED

    Adderall XR/Amphetamine Aspartate, Amphetamine Sulfate, Dextroamphetamine Saccharate, Dextroamphetamine Sulfate/Amphetamine, Dextroamphetamine Oral Cap ER: 5mg, 10mg, 15mg, 20mg, 25mg, 30mg
    Adderall/Amphetamine Aspartate, Amphetamine Sulfate, Dextroamphetamine Saccharate, Dextroamphetamine Sulfate/Amphetamine, Dextroamphetamine Oral Tab: 5mg, 7.5mg, 10mg, 12.5mg, 15mg, 20mg, 30mg

    DOSAGE & INDICATIONS

    For the treatment of attention-deficit hyperactivity disorder (ADHD).
    Oral dosage (immediate-release tablets; e.g., Adderall)
    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 60 mg/day PO are not usually needed. Dosage should be individualized; use lowest effective dose after stabilization. Lack of response to one stimulant does not predict a response to other stimulants. ADHD is a chronic condition that requires ongoing management and monitoring. Treatment strategies must be individualized for patients based on psychosocial and comorbid factors. In treatment guidelines, stimulants are considered first-line therapy in the treatment of ADHD.

    Children and Adolescents 6 years and older

    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. Although FDA-approved labeling states doses greater than 40 mg/day are rarely necessary, some experts recommend a max dose of 60 mg/day in patients weighing more than 50 kg. Dosage should be individualized; use lowest effective dose after stabilization. Lack of response to one stimulant does not predict a response to other stimulants. ADHD is a chronic condition that will require ongoing management and monitoring. Sixty to eighty percent of children will continue to need treatment in adulthood. The effect of behavioral therapy is controversial; however, combined drug and behavioral therapy has been shown to be more effective than behavioral therapy alone. In many cases, drug treatment alone showed a consistent dose-sensitive effect in improving core ADHD symptoms. Treatment strategies must be individualized for patients based on psychosocial and comorbid factors. In treatment guidelines, stimulants are considered first-line therapy in the treatment of ADHD.

    Children 3 to 5 years

    2.5 mg PO once daily in the morning. May titrate daily dose in 2.5 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. Maximum dosage information is not available; however, doses should not exceed 40 mg/day, the maximum recommended dose for children ages 6 to 12 years. Although this dosing information is available in the FDA-approved package labeling, the American Academy of Pediatrics (AAP) does not recommend the use of amphetamine; dextroamphetamine in this age group due to lack of safety and efficacy data.

    Oral dosage (extended-release capsules; e.g., Adderall XR)
    Adults

    When initiating treatment for the first time or switching from another ADHD medication, the recommended dose is 20 mg/day PO once daily upon awakening. Patients taking divided doses of the immediate-release formulation may be switched to the extended-release formulation once daily at the same total daily dose. Adjust at weekly intervals if needed. Because Adderall XR has not been formally evaluated in geriatric patients, dosage recommendations are not available from the manufacturer in this patient population. Dose should be based on individual response and tolerability; use lowest effective dose after stabilization. Lack of response to one stimulant does not predict a response to other stimulants. ADHD is a chronic condition that will require ongoing management and monitoring. Treatment strategies must be individualized for patients based on psychosocial and comorbid factors. In treatment guidelines, stimulants are considered first-line therapy in the treatment of ADHD.

    Adolescents

    Initially, 10 mg PO once daily in the morning for both initial therapy and when converting to extended-release amphetamine; dextroamphetamine from another stimulant medication. May titrate daily dose to 20 mg/day after 1 week if ADHD symptoms are not adequately controlled. Patients taking divided doses of immediate-release amphetamine; dextroamphetamine may switch to the extended-release formulation PO once daily at the same total daily dose. The maximum recommended dose is 30 mg/day; doses of the XR formulations greater than 30 mg/day have not been studied in pediatric patients. Dosage should be individualized; use lowest effective dose after stabilization. Lack of response to one stimulant does not predict a response to other stimulants. ADHD is a chronic condition that will require ongoing management and monitoring. Sixty to eighty percent of children will continue to need treatment in adulthood. The effect of behavioral therapy is controversial; however, combined drug and behavioral therapy has been shown to be more effective than behavioral therapy alone. In many cases, drug treatment alone showed a consistent dose-sensitive effect in improving core ADHD symptoms. Treatment strategies must be individualized for patients based on psychosocial and comorbid factors. In treatment guidelines, stimulants are considered first-line therapy in the treatment of ADHD.

    Children 6 to 12 years

    Initially, 5 mg to 10 mg PO once daily in the morning. If converting to extended-release amphetamine; dextroamphetamine from a different stimulant medication, begin with 10 mg PO once daily. May titrate daily dose in 5 mg to 10 mg increments at weekly intervals to the minimum effective dose. May titrate in 5 mg to 10 mg increments at weekly intervals to the minimum effective dose. Patients taking divided doses of immediate-release amphetamine; dextroamphetamine may switch to the extended-release formulation PO once daily at the same total daily dose. The FDA-approved maximum dose for the XR formulation is 30 mg/day. Dosage should be individualized; use lowest effective dose after stabilization. Lack of response to one stimulant does not predict a response to other stimulants. ADHD is a chronic condition that will require ongoing management and monitoring. Sixty to eighty percent of children will continue to need treatment in adulthood. The effect of behavioral therapy is controversial; however, combined drug and behavioral therapy has been shown to be more effective than behavioral therapy alone. In many cases, drug treatment alone showed a consistent dose-sensitive effect in improving core ADHD symptoms. Treatment strategies must be individualized for patients based on psychosocial and comorbid factors. In treatment guidelines, stimulants are considered first-line therapy in the treatment of ADHD.

    For the treatment of narcolepsy.
    Oral dosage (immediate-release tablets; e.g., Adderall)
    Adults, Adolescents, and Children 12 years and older

    Initially, 10 mg PO once daily in the morning. 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 10 mg/day at weekly intervals to the minimum effective dose. Maximum: 60 mg/day. Adjust dose requirements based on individual response. If bothersome adverse reactions appear (e.g., insomnia or anorexia), the dosage should be reduced.

    Children 6 to 11 years

    Initially, 5 mg PO once daily in the morning. 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. If insomnia or anorexia appear, reduce dosage. Max: 60 mg/day.

    For the short-term treatment (i.e., 3 to 6 weeks) of exogenous obesity† as an adjunct to dietary modification and exercise.
    Oral dosage
    Adults

    The usual daily dosage range is 5 mg/day to 30 mg/day PO, administered as 5 mg/dose to 10 mg/dose 30 to 60 minutes before meals. Adjust based on individual response. For short-term (3 to 6 weeks) treatment only. NOTE: Therapy is considered only as an adjunct to diet and exercise; without these modifications weight gain resumes after drug discontinuation. Based on clinical trials, the anorectic effect is greater in the first few weeks of therapy and tends to decrease in subsequent weeks. The long-term effectiveness of these agents is limited.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    60 mg/day PO for ADHD or narcolepsy for immediate-release tablets; 30 mg/day PO for obesity using immediate-release tablets. 20 mg/day PO using extended-release capsules for ADHD.

    Geriatric

    60 mg/day PO for ADHD or narcolepsy for immediate-release tablets; 30 mg/day PO for obesity using immediate-release tablets. The extended-release capsules have not been formally evaluated in the elderly.

    Adolescents

    40 mg/day PO for ADHD or 60 mg/day PO for narcolepsy using immediate-release tablets; some experts recommend an off-label maximum of 60 mg/day PO if weight > 50 kg for the treatment of ADHD. 20 mg/day PO using extended-release capsules.

    Children

    >= 6 years: 40 mg/day PO for ADHD or 60 mg/day PO for narcolepsy using immediate-release tablets; some experts recommend an off-label maximum of 60 mg/day PO if weight > 50 kg for the treatment of ADHD. 30 mg/day PO using extended-release capsules.
    3—5 years: Maximum dosage information is not provided by FDA-approved labeling; doses should not exceed 40 mg/day PO for immediate-release tablets. Do not use extended-release capsules.
    < 3 years: Safety and efficacy have not been established.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; the manufacturer states that hepatic dysfunction has the potential to inhibit the elimination of amphetamine and result in prolonged exposures; use caution.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; the manufacturer states that renal dysfunction has the potential to inhibit the elimination of amphetamine and result in prolonged exposures; use caution.

    ADMINISTRATION

    NOTE: A MedGuide is available which informs patients about the cardiac and psychiatric risks associated with use, and should be provided by the authorized dispenser to each patient receiving a prescription.

    Oral Administration
    Oral Solid Formulations

    Immediate-release tablets: 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.
    Extended-release capsules: Administer dose once daily upon awakening. Do not crush or chew the capsule or capsule contents (beads). If swallowing is difficult, the capsule may be opened and the entire contents gently sprinkled on a spoonful of cool applesauce and swallowed immediately (do not store for future use). Follow with a drink of water or other liquid.

    STORAGE

    Adderall:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Adderall XR:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Amphetamine; dextroamphetamine combinations are contraindicated for use in patients with known hypersensitivity to the sympathomimetic amines or any component of these products.
    Amphetamines are associated with a reduced appetite and weight loss. Over time weight will increase but not to the amount expected based on CDC normative values. In adolescents, mean weight change from baseline within the initial 4 weeks of therapy was -1.1 pounds and -2.8 pounds, respectively, for patients receiving 10 mg and 20 mg Adderall XR. Higher doses were associated with greater weight loss within the initial 4 weeks of treatment.

    Alcoholism, substance abuse

    Amphetamine; dextroamphetamine is contraindicated in patients with a history of substance abuse. Evaluate the child or adult patient for a history (or a family history of) abuse of prescription medicines or street drugs, or abuse or dependence on alcohol (alcoholism). Amphetamine; dextroamphetamine combinations have a high potential for abuse. Administration of amphetamines for a prolonged period of time may lead to physical and psychological drug dependence. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Symptoms of chronic intoxication include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders.

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

    Amphetamine; dextroamphetamine combinations are contraindicated in patients in an agitated state. Stimulants such as amphetamine; dextroamphetamine should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur in such patients. 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, amphetamine; 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 post-marketing 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

    Amphetamine; dextroamphetamine is contraindicated in patients with symptomatic cardiovascular disease, advanced atherosclerosis, and moderate to severe hypertension. However, patients with even mild hypertension or tachycardia should be closely monitored while taking amphetamines. Use stimulant medications with caution in patients for whom an elevation in blood pressure or heart rate may be clinically significant. 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. Elevated blood pressure may require a dose reduction, discontinuation, and/or initiation of appropriate antihypertensive medication. Periodic blood pressure and heart rate monitoring is recommended in all patients taking stimulant medications. Adolescents with ADHD were enrolled in a 4-week controlled comparative trial of Adderall XR vs. placebo; 7 of 64 (11%) placebo-treated patients and 7 of 100 (7%) patients receiving Adderall XR had elevations in systolic blood pressures > 15 mmHg. Dose-related blood pressure elevations have also been noted in single dose studies. All increases were transient, appeared maximal at 2 to 4 hours post dose and were not associated with symptoms.

    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 ...

    Amphetamine; dextroamphetamine is contraindicated in patients with symptomatic cardiac disease, advanced arteriosclerosis, and moderate to severe hypertension. The FDA recommends that, in general, stimulant medications not be used in patients with known serious cardiac structural abnormalities, a history of acute myocardial infarction, aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, ventricular dysfunction or heart failure, cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. Stimulant medications may increase blood pressure or heart rate in some individuals; more serious cardiac effects have also been associated with stimulant use. Sudden unexplained death (SUD) and myocardial infarction have occurred in adults receiving stimulants at standard dosages for attention-deficit hyperactivity-disorder (ADHD). Sudden death has also been associated with stimulant medications at usual doses in pediatrics with structural cardiac abnormalities or other serious heart problems. A large retrospective cohort study including over 1.2 million children and young adults 2—24 years of age did not find an increased risk of serious cardiovascular events in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiovascular disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The American Heart Association (AHA) states that it is reasonable to consider the use of these medications 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) > 0.46 sec, or heart rate or blood pressure > 2 SD above the mean for age. All patients being considered for treatment with stimulant medications should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmias, 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 is reasonable 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 stimulant medication. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history.

    Cerebrovascular disease, stroke

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

    Children, growth inhibition, infants

    Children 3 years of age and older have been successfully treated for attention-deficit hyperactivity-disorder (ADHD) with amphetamines. It should be noted that not all children with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy. Amphetamines are not recommended for use in children and infants younger than 3 years of age, and should not be used for treating obesity in children younger than 12 years of age. Do not use the extended-release capsule formulation in children younger than 6 years of age, as safety and efficacy are not established. However, the efficacy of stimulant therapy in children with ADHD is substantiated by a large body of evidence. Monitoring of the effectiveness of stimulant therapy by the health care prescriber, parents, and teachers is important; periodic reassessment of the need for medication is recommended. Appropriate stimulant therapy should not suppress normal emotions or intellectual ability in the child or adolescent; the occurrence of certain side effects may indicate a need for dosage reduction. In psychotic children, amphetamines may exacerbate behavioral disturbances, psychosis, or thought disorders. New onset psychotic or manic symptoms may develop in children and adolescents receiving therapeutic doses of stimulants. Discontinuation of therapy may be required. Although a direct causal relationship has not been established, aggressive behavior and hostility have been reported during use of some stimulants for ADHD in children. IIt is recommended to monitor for signs of aggression or worsening of pre-existing aggressive behavior when treatment is initiated. 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 obtained on the effects of the stimulants on growth suppression in children 7 to 10 years of age suggested that regularly medicated children (7 days/week) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years. The long-term effects of stimulants on brain development and physical growth in children are unknown. Sudden death has been reported in association with CNS stimulant treatment at usual doses in children with structural cardiac abnormalities or other serious heart problems (i.e., aortic stenosis, cardiomyopathy, congenital heart disease, prosthetic heart valves, valvular heart disease, ventricular dysfunction). Some case reports have involved concomitant medications, such as tricyclic antidepressants. A large retrospective cohort study including over 1.2 million children and young adults 2 to 24 years of age did not find an increased risk of serious cardiovascular events, including sudden cardiac death, myocardial infarction, or stroke in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31 to 1.85). The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. Although some structural cardiac abnormalities alone may carry an increased risk of sudden death, stimulant products generally should not be used in patients with known structural cardiac abnormalities or other serious heart conditions. Exceptions to this warning do exist, but careful screening and monitoring is recommended by the American Heart Association (see separate paragraph detailing cardiac contraindications and precautions).

    Hyperthyroidism, thyrotoxicosis

    Amphetamine; dextroamphetamine is contraindicated for use patients with hyperthyroidism, including thyrotoxicosis, since sympathomimetic stimulation may induce cardiac arrhythmias or other side effects.

    Glaucoma, visual disturbance

    Amphetamine; dextroamphetamine is contraindicated in patients with glaucoma. The sympathetic stimulation of amphetamines blocks aqueous outflow and raises intraocular pressure. Occasionally, visual disturbance, such as blurred vision and accommodation difficulties, have been reported in individuals without ocular disease while they are taking amphetamine; dextroamphetamine. Patients should report any new visual disturbance as ophthalmic evaluation may be needed.

    Breast-feeding

    Amphetamines are excreted in human breast milk by the lactating mother. According to the manufacturer, it is advisable to avoid breast-feeding during the use of amphetamines. Concentrations in breast-milk are often more concentrated than plasma levels. Breast milk concentrations in one woman taking 20 mg daily of racemic amphetamine ranged from 55 to 138 ng/mL with milk to plasma ratios of 2.8 to 7.5. The infant was monitored for 24 months and no adverse effects from amphetamine exposure were noted. Methylphenidate may be considered an alternative to amphetamine agents in women who are breast-feeding an infant, although the medical use of stimulant medications has not been formally evaluated during lactation. The AAP previously considered amphetamines, when used as drugs of abuse, to be contraindicated in breast-feeding due to concerns of irritability and poor sleeping pattern in the infant. 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. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

    Neonates, pregnancy

    Amphetamine; dextroamphetamine combinations are classified in FDA pregnancy risk category C. Amphetamine; dextroamphetamine combinations should only be used during pregnancy if the expected benefit to the mother clearly outweighs the potential fetal risk. There is one case of a neonate born with a severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia following maternal exposure to dextroamphetamine sulfate and lovastatin during the first trimester of pregnancy. 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 1898 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 known to occur in human neonates who are born to mothers dependent on amphetamines include increased incidences of premature births, low birth weights and length, lower occipitofrontal circumference, and physical withdrawal symptoms (e.g., abnormal sleep patterns, 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 newborns as assessed by cranial ultrasonography. The authors speculated that the ultrasonographic abnormalities were probably related to the vasoconstrictive properties of the drugs. The effects of amphetamines during labor and delivery are unknown.

    Tics, Tourette's syndrome

    Amphetamine; dextroamphetamine may precipitate motor or phonetic tics in those with Tourette's syndrome. Some patients with Tourette's syndrome may actually benefit from stimulant therapy; administer under close supervision.

    Driving or operating machinery

    The use of amphetamine; dextroamphetamine 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.

    Seizure disorder, seizures

    Use amphetamine; dextroamphetamine with caution in patients with 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.

    Surgery

    The use of inhalational anesthetics during surgery may sensitize the myocardium to the effects of amphetamines and other sympathomimetic drugs.

    Radiographic contrast administration

    Amphetamines lower the seizure threshold. 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.

    Abrupt discontinuation

    Abrupt discontinuation of amphetamine; dextroamphetamine after chronic use is not recommended. Discontinuation may unmask severe mental depression or extreme fatigue, or precipitate withdrawal symptoms. Gradual withdrawal of therapy is recommended.

    Geriatric

    Amphetamine; dextroamphetamine has not been systematically studied in the geriatric population for use in 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 titrated with low doses initially and with a slow increase. 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. According to the Beers Criteria, stimulants such as amphetamines are considered potentially inappropriate medications (PIMs) for use in geriatric patients with insomnia and should be avoided due to the potential for drug-induced CNS stimulant effects.

    Hypercortisolism

    Amphetamine; dextroamphetamine may cause hypercortisolism, as amphetamines can cause a significant elevation in plasma corticosteroid concentrations. The elevation is greatest in the evening. Amphetamines may interfere with urinary steroid determinations; consider the possible effect of amphetamine; dextroamphetamine if determination of plasma corticosteroid concentrations is desired.

    Hepatic disease, renal impairment

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

    MAOI therapy

    Amphetamine; dextroamphetamine is contraindicated in patients who have received MAOI therapy within the past 14 days. MAOI antidepressants slow amphetamine metabolism, potentiating their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings. This may precipitate hypertensive crisis, malignant hyperthermia, and a variety of toxic neurologic effects; these events can be fatal.

    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.

    Anorexia nervosa, bulimia nervosa, obesity treatment

    Obesity treatment with amphetamine; dextroamphetamine should be initiated only in weight reduction programs for patients in whom alternative therapies, including repeated dietary reduction, exercise, or other medications have been ineffective. 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 increase their susceptibility to the adverse effects of stimulants. In addition, the abuse potential of stimulants in weight loss induction should be considered in patients with an eating disorder.

    ADVERSE REACTIONS

    Severe

    rhabdomyolysis / Delayed / 0-1.0
    Tourette's syndrome / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    stroke / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    priapism / Delayed / Incidence not known
    seizures / Delayed / 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
    ocular hypertension / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    coma / Early / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known

    Moderate

    sinus tachycardia / Rapid / 6.0-6.0
    constipation / Delayed / 2.0-4.0
    palpitations / Early / 2.0-4.0
    impotence (erectile dysfunction) / Delayed / 2.0-4.0
    psychosis / Early / 0.1-0.1
    mania / Early / 0.1-0.1
    teeth grinding (bruxism) / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    dysphoria / Early / Incidence not known
    euphoria / Early / Incidence not known
    dyskinesia / Delayed / Incidence not known
    supranormalization / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    peripheral vasoconstriction / Rapid / Incidence not known
    skin ulcer / Delayed / Incidence not known
    hallucinations / Early / Incidence not known
    formication / Early / Incidence not known
    hostility / Early / Incidence not known
    depression / Delayed / Incidence not known
    delirium / Early / Incidence not known
    hyperreflexia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hyperthermia / Delayed / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    psychological dependence / Delayed / Incidence not known
    tolerance / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    physiological dependence / Delayed / Incidence not known

    Mild

    anorexia / Delayed / 22.0-36.0
    xerostomia / Early / 2.0-35.0
    insomnia / Early / 12.0-27.0
    headache / Early / 26.0-26.0
    abdominal pain / Early / 11.0-14.0
    weight loss / Delayed / 4.0-11.0
    emotional lability / Early / 2.0-9.0
    nausea / Early / 2.0-8.0
    anxiety / Delayed / 8.0-8.0
    agitation / Early / 8.0-8.0
    vomiting / Early / 2.0-7.0
    dizziness / Early / 2.0-7.0
    diarrhea / Early / 6.0-6.0
    fatigue / Early / 2.0-6.0
    fever / Early / 0-5.0
    dyspepsia / Early / 2.0-4.0
    dysmenorrhea / Delayed / 2.0-4.0
    libido decrease / Delayed / 2.0-4.0
    hyperhidrosis / Delayed / 2.0-4.0
    photosensitivity / Delayed / 2.0-4.0
    drowsiness / Early / 2.0-4.0
    dental caries / Delayed / 0-4.0
    infection / Delayed / 2.0-4.0
    dysgeusia / Early / Incidence not known
    libido increase / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    alopecia / Delayed / Incidence not known
    restlessness / Early / Incidence not known
    tremor / Early / Incidence not known
    mydriasis / Early / Incidence not known
    irritability / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acarbose: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Acebutolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Acetaminophen; Aspirin, ASA; Caffeine: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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; Butalbital; Caffeine: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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; Butalbital; Caffeine; Codeine: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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; Tramadol: The risk of seizures from the use of tramadol may be increased with concomitant use of CNS stimulants and anorectics that may induce seizures, including the amphetamines. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Acetazolamide: Concurrent use of amphetamines and urinary alkalinizers, such as acetazolamide and methazolamide, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Albiglutide: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Albuterol: Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Albuterol; Ipratropium: Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Alfuzosin: 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.
    Aliskiren; Amlodipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Aliskiren; Hydrochlorothiazide, HCTZ: 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.
    Aliskiren; Valsartan: 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 or the selection of alternative therapeutic agents may be needed.
    Alkalinizing Agents: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Alogliptin: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving alogliptin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Alogliptin; Metformin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving alogliptin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Alogliptin; Pioglitazone: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving alogliptin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Alpha-glucosidase Inhibitors: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Aluminum Hydroxide: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Aluminum Hydroxide; Magnesium Carbonate: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Aluminum Hydroxide; Magnesium Hydroxide: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Aluminum Hydroxide; Magnesium Trisilicate: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Amantadine: Amantadine used concomitantly with psychostimulants can result in increased stimulant effects, such as nervousness, irritability, or insomnia, and can lead to seizures or cardiac arrhythmias. Close monitoring of the patient is recommended.
    Ambrisentan: Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amiloride; Hydrochlorothiazide, HCTZ: 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.
    Amlodipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine; Atorvastatin: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine; Benazepril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: 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 or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: 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 or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Amlodipine; Olmesartan: 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 or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine; Telmisartan: 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 or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine; Valsartan: 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 or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Ammonium Chloride: 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: 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: 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 or the selection of alternative therapeutic agents may be needed.
    Angiotensin-converting enzyme inhibitors: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Antacids: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Arformoterol: 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.
    Aripiprazole: 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.
    Armodafinil: 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.
    Ascorbic Acid, Vitamin C: Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should beused with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. 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.
    Asenapine: 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.
    Aspirin, ASA; Butalbital; Caffeine: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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.
    Atenolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Atenolol; Chlorthalidone: 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. 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Atomoxetine: Amphetamines increase both systolic and diastolic blood pressure; atomoxetine has been reported to also increase blood pressure and heart rate, probably via inhibition of norepinephrine reuptake. Due to an additive pharmacodynamic effect, amphetamine; dextroamphetamine combinations and atomoxetine should be used together cautiously, particularly in patients with a history of cardiac disease. Consider monitoring heart rate and blood pressure at baseline and regularly throughout treatment if these agents must be used together.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: 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. Theoretically, concurrent use of methylene blue and amphetamines may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and amphetamines increase central serotonin effects. 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 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. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: 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.
    Azilsartan: 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 or the selection of alternative therapeutic agents may be needed.
    Azilsartan; Chlorthalidone: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: 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. 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: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Benazepril; Hydrochlorothiazide, HCTZ: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Bendroflumethiazide; Nadolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: 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. Theoretically, concurrent use of methylene blue and amphetamines may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and amphetamines increase central serotonin effects. 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 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. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Beta-blockers: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Betaxolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Bethanechol: Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
    Bisoprolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Bisoprolol; Hydrochlorothiazide, HCTZ: 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. 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Brimonidine; Timolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Bromocriptine: 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.
    Budesonide; Formoterol: Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Bupropion: Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary.
    Bupropion; Naltrexone: Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary.
    Cabergoline: In theory, an interaction is possible between cabergoline, an ergot derivative, and some sympathomimetic agents such as amphetamines. Use of the ergot derivative bromocriptine for lactation suppression in conjunction with a sympathomimetic (i.e., isometheptene or phenylpropanolamine) for other therapeutic uses has resulted in adverse effects such as worsening headache, hypertension, ventricular tachycardia, seizures, sudden loss of vision, and cerebral vasospasm.
    Caffeine: Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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.
    Caffeine; Ergotamine: 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. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of the amphetamine salts. 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: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Calcium Carbonate; Magnesium Hydroxide: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Calcium Carbonate; Risedronate: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Calcium; Vitamin D: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Calcium-channel blockers: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Canagliflozin: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving canagliflozin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Canagliflozin; Metformin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving canagliflozin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Candesartan: 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 or the selection of alternative therapeutic agents may be needed.
    Candesartan; Hydrochlorothiazide, HCTZ: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Captopril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Captopril; Hydrochlorothiazide, HCTZ: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Carbamazepine: 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.
    Carbidopa; Levodopa: Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions of amphetamines are recommended if the two agents are used concurrently.
    Carbidopa; Levodopa; Entacapone: Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions of amphetamines are recommended if the two agents are used concurrently.
    Cardiac glycosides: Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics.
    Carteolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Carvedilol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Chlorothiazide: 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.
    Chlorthalidone: 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.
    Chlorthalidone; Clonidine: 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. Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Chondroitin; Glucosamine: Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should beused with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. 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.
    Citalopram: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Citric Acid; Potassium Citrate: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Citric Acid; Potassium Citrate; Sodium Citrate: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Citric Acid; Sodium Citrate: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Clevidipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Clobazam: 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.
    Clonazepam: Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamine; dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Clonidine: Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Clozapine: 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.
    Codeine; Phenylephrine; Promethazine: Amphetamines may pharmacodynamically counteract the sedative properties of promethazine. 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.
    Codeine; Promethazine: Amphetamines may pharmacodynamically counteract the sedative properties of promethazine. 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.
    Colchicine: The response to sympathomimetics may be enhanced by colchicine.
    Collagenase: Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should beused with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. 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.
    Cranberry, Vaccinium macrocarpon Ait.: Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should beused with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. 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.
    Dapagliflozin: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving dapagliflozin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Dapagliflozin; Metformin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving dapagliflozin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Patients receiving amphetamines may experience prolonged effects if receiving ritonavir concurrently. A case report describes a patient who was treated with ritonavir and saquinavir and then experienced a prolonged effect from a small dose of methylene-dioxy-methamphetamine (MDMA or ecstasy) and a near fatal reaction from a small dose of gamma-hydroxybutyrate (GHB). The effects in this patient suggests that the prolonged effects of MDMA were due to ritonavir-induced inhibition of CYP2D6 metabolism. The GHB toxicity in this patient may have been due to ritonavir-induced inhibition of first pass metabolism, leading to increased levels of GHB. Patients receiving other amphetamine drugs, such as amphetamine, amphetamine; dextroamphetamine mixed salts, lisdexamfetamine, or methamphetamine may experience prolonged effects if receiving ritonavir concurrently. Patients should be warned that there are potentially serious drug interactions between ritonavir and illicit drugs, such as ecstasy.
    Delavirdine: Delavirdine is a known potent inhibitor of cytochrome P-450 2D6. Patients receiving amphetamine or dextroamphetamine should be monitored closely for toxicity if delavirdine treatment is added.
    Desiccated Thyroid: 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.
    Desvenlafaxine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as amphetamines. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. A man developed marked agitation, anxiety, diaphoresis, shivering, tachycardia, tremor, generalized hypertonia, hyperreflexia, 1 to 2 beats of inducible ankle clonus, frequent myoclonic jerking, and tonic spasm of the right side of his orbicularis oris muscle while taking dexamphetamine and venlafaxine. Cessation of both drugs and administration of cyproheptadine led to a stepwise heart rate reduction and complete symptom resolution. Patients receiving SNRIs and amphetamines should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The SNRI and amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Dexmethylphenidate: The stimulant effects of dexmethylphenidate can be additive when used concurrently with most other psychostimulants. Do not give dexmethylphenidate along with amphetamines since these are duplicate therapies and may result in overdosage. The combination of dexmethylphenidate with other CNS stimulants may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. The stimulant effects of methylphenidate can be additive when used concurrently with most other psychostimulants. In general the use of methylphenidate with the amphetamines would not be recommended, to avoid duplicate therapies. The combination of methylphenidate with amphetamine may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems.
    Dextromethorphan; Promethazine: Amphetamines may pharmacodynamically counteract the sedative properties of promethazine. 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.
    Diazepam: 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.
    Digitoxin: Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics.
    Digoxin: Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics.
    Dihydroergotamine: 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: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Dorzolamide; Timolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Doxazosin: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Dronabinol, THC: 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: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Duloxetine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as amphetamines. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. A man developed marked agitation, anxiety, diaphoresis, shivering, tachycardia, tremor, generalized hypertonia, hyperreflexia, 1 to 2 beats of inducible ankle clonus, frequent myoclonic jerking, and tonic spasm of the right side of his orbicularis oris muscle while taking dexamphetamine and venlafaxine. Cessation of both drugs and administration of cyproheptadine led to a stepwise heart rate reduction and complete symptom resolution. Patients receiving SNRIs and amphetamines should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The SNRI and amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Dutasteride; Tamsulosin: 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.
    Dyphylline: Coadministration of dyphylline with sympathomimetics should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias, and should be avoided if possible.
    Dyphylline; Guaifenesin: Coadministration of dyphylline with sympathomimetics should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias, and should be avoided if possible.
    Empagliflozin: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving empagliflozin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Empagliflozin; Linagliptin: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving empagliflozin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving linagliptin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Empagliflozin; Metformin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving empagliflozin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Enalapril, Enalaprilat: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Enalapril; Felodipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Enalapril; Hydrochlorothiazide, HCTZ: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Enflurane: 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.
    Eplerenone: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as eplerenone. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Epoprostenol: Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Eprosartan: 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 or the selection of alternative therapeutic agents may be needed.
    Eprosartan; Hydrochlorothiazide, HCTZ: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Ergoloid Mesylates: 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: 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: 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: 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.
    Escitalopram: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Eslicarbazepine: 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: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Ethanol: Amphetamines do not change the pharmacokinetics of ethanol nor do they relieve cognitive impairment that results from ethanol intoxication, even though subjective improvements in motor performance have been noted on concomitant ingestion by patients. Ethanol containing beverages generally should be avoided.
    Ethotoin: Amphetamine or dextroamphetamine may delay the intestinal absorption of orally-administered phenytoin; the extent of phenytoin absorption is not known to be effected. Monitor the patient's neurologic status closely, as the amphetamines may also lower the seizure threshold in some patients on phenytoin or fosphenytoin.
    Etomidate: 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: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Ezogabine: 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.
    Felbamate: 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.
    Felodipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Fluoxetine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Fluoxetine; Olanzapine: 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. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Fluticasone; Salmeterol: Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Fluticasone; Vilanterol: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Food: Avoid administering marijuana and amphetamines together as concurrent use may result in adverse cardiovascular effects, such as tachycardia and cardiac arrhythmias. Marijuana is known to produce significant increases in heart rate and cardiac output lasting for 2-3 hours. Further, rare case reports of myocardial infarction and cardiac arrhythmias have been associated with marijuana use. Amphetamines have also been reported to produce a wide range of cardiovascular effects including cardiac arrhythmias, palpitations, and sinus tachycardia. Coadministration of marijuana with amphetamines may result in significant cardiovascular adverse events and thus, should be avoided. 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. 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: Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Formoterol; Mometasone: Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Fosinopril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Fosinopril; Hydrochlorothiazide, HCTZ: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Fosphenytoin: Amphetamine or dextroamphetamine may delay the intestinal absorption of orally-administered phenytoin; the extent of phenytoin absorption is not known to be effected. Monitor the patient's neurologic status closely, as the amphetamines may also lower the seizure threshold in some patients on phenytoin or fosphenytoin.
    Gabapentin: 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, discontinue use of amphetamines.
    Glimepiride; Pioglitazone: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Glimepiride; Rosiglitazone: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Glipizide; Metformin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Glyburide; Metformin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Glycopyrrolate; Formoterol: Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Green Tea: 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.
    Guanabenz: Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Patients should be monitored for loss of blood pressure control.
    Guanfacine: Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Guarana: Caffeine, an active constituent of guarana, is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Use of guarana should be avoided with amphetamine, dextroamphetamine, methylphenidate, modafinil, pemoline, pseudoephedrine, beta-agonists or other sympathomimetics. When combined with any of these medications, nervousness, irritability, insomnia, and/or cardiac arrhythmias may result.
    Haloperidol: 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.
    Halothane: 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.
    Hydantoins: Amphetamine or dextroamphetamine may delay the intestinal absorption of orally-administered phenytoin; the extent of phenytoin absorption is not known to be effected. Monitor the patient's neurologic status closely, as the amphetamines may also lower the seizure threshold in some patients on phenytoin or fosphenytoin.
    Hydralazine; Hydrochlorothiazide, HCTZ: 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.
    Hydrochlorothiazide, HCTZ: 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.
    Hydrochlorothiazide, HCTZ; Irbesartan: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Hydrochlorothiazide, HCTZ; Lisinopril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Hydrochlorothiazide, HCTZ; Losartan: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Hydrochlorothiazide, HCTZ; Methyldopa: 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.
    Hydrochlorothiazide, HCTZ; Metoprolol: 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. 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Hydrochlorothiazide, HCTZ; Moexipril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Hydrochlorothiazide, HCTZ; Olmesartan: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Hydrochlorothiazide, HCTZ; Propranolol: 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. 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Hydrochlorothiazide, HCTZ; Quinapril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. 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.
    Hydrochlorothiazide, HCTZ; Spironolactone: 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.
    Hydrochlorothiazide, HCTZ; Telmisartan: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Hydrochlorothiazide, HCTZ; Triamterene: 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.
    Hydrochlorothiazide, HCTZ; Valsartan: 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 or the selection of alternative therapeutic agents may be needed. 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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: 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. Theoretically, concurrent use of methylene blue and amphetamines may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and amphetamines increase central serotonin effects. 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 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. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Ibritumomab Tiuxetan: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Iloperidone: 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.
    Iloprost: Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Incretin Mimetics: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Indacaterol: Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Caution and close observation is needed if indacaterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Indacaterol; Glycopyrrolate: Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Caution and close observation is needed if indacaterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Indapamide: Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Insulin Degludec; Liraglutide: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Insulins: Monitor patients receiving insulin closely for worsening glycemic control when sympathomimetic agents are instituted. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism.
    Irbesartan: 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 or the selection of alternative therapeutic agents may be needed.
    Isocarboxazid: In general, all types of sympathomimetics and psychostimulants 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 even 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: 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: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Ketamine: 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.
    Labetalol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Lacosamide: 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.
    Lamotrigine: 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.
    Levalbuterol: Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Levetiracetam: 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.
    Levobetaxolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Levobunolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Levodopa: Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions of amphetamines are recommended if the two agents are used concurrently.
    Levomilnacipran: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as amphetamines. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. A man developed marked agitation, anxiety, diaphoresis, shivering, tachycardia, tremor, generalized hypertonia, hyperreflexia, 1 to 2 beats of inducible ankle clonus, frequent myoclonic jerking, and tonic spasm of the right side of his orbicularis oris muscle while taking dexamphetamine and venlafaxine. Cessation of both drugs and administration of cyproheptadine led to a stepwise heart rate reduction and complete symptom resolution. Patients receiving SNRIs and amphetamines should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The SNRI and amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Levothyroxine: 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.
    Linagliptin: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving linagliptin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Linagliptin; Metformin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving linagliptin should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted.
    Linezolid: Amphetamines should not be administered during or within 14 days following the use of linezolid. Linezolid possesses MAO-inhibiting activity and can prolong and intensify the cardiac stimulation and vasopressor effects of the amphetamines. Linezolid has the potential for interaction with adrenergic and serotonergic agents, which may increase the risk for serotonin syndrome. Serotonin syndrome symptoms may include 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, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). If serotonin syndrome occurs, discontinue the amphetamine and any concomitant serotonergic drugs.
    Liothyronine: 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.
    Liotrix: 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: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Lisinopril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Lithium: Amphetamines (e.g., amphetamine, dextroamphetamine, lisdexamfetamine, methamphetamine) can occasionally worsen mania in those with bipolar disorder, potentially reducing the overall effectiveness of treatment with mood stabilizers. According to some literature and the product labeling of many stimulants, lithium may antagonize the anorectic and stimulant effects of amphetamines. Despite this precaution, some data, including consensus guidelines, indicate a beneficial effect when using stimulants in combination with mood stabilizers in patients with refractory bipolar depression. Further study is needed to fully assess the benefits and risks that may occur from concomitant administration of amphetamines and lithium. Close monitoring is advisable when combination therapy is initiated or dosages are increased.
    Loop diuretics: Amphetamines 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 or the selection of alternative therapeutic agents may be needed.
    Lopinavir; Ritonavir: Patients receiving amphetamines may experience prolonged effects if receiving ritonavir concurrently. A case report describes a patient who was treated with ritonavir and saquinavir and then experienced a prolonged effect from a small dose of methylene-dioxy-methamphetamine (MDMA or ecstasy) and a near fatal reaction from a small dose of gamma-hydroxybutyrate (GHB). The effects in this patient suggests that the prolonged effects of MDMA were due to ritonavir-induced inhibition of CYP2D6 metabolism. The GHB toxicity in this patient may have been due to ritonavir-induced inhibition of first pass metabolism, leading to increased levels of GHB. Patients receiving other amphetamine drugs, such as amphetamine, amphetamine; dextroamphetamine mixed salts, lisdexamfetamine, or methamphetamine may experience prolonged effects if receiving ritonavir concurrently. Patients should be warned that there are potentially serious drug interactions between ritonavir and illicit drugs, such as ecstasy.
    Lorazepam: 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.
    Lorcaserin: The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Co-use of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome.
    Losartan: 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 or the selection of alternative therapeutic agents may be needed.
    Loxapine: 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: 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: Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy if taking macitentan with a sympathomimetic.
    Magnesium Hydroxide: Concurrent use of amphetamines and gastrointestinal alkalinizers, such as antacids (e.g., calcium carbonate, magnesium oxide, sodium bicarbonate), should be avoided. An alkaline environment increases the absorption of amphetamines. In addition, antacids act as urinary alkalinizers, which diminishes the urinary excretion of amphetamines. Urinary alkalinizers increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs.
    Maprotiline: Sympathomimetics may interact with maprotiline, resulting in severe cardiovascular effects including arrhythmias, severe hypertension, hyperpyrexia, and/or severe headaches.
    Mecasermin rinfabate: Amphetamine/Dextroamphetamine may cause suppression of growth which could result in mecasermin treatment failure as growth rate increases may be suppressed. If concomitant use of these agents is necessary, practitioners should monitor height and weight parameters relative to age at the initiation of treatment and periodically during therapy.
    Mecasermin, Recombinant, rh-IGF-1: Amphetamine/Dextroamphetamine may cause suppression of growth which could result in mecasermin treatment failure as growth rate increases may be suppressed. If concomitant use of these agents is necessary, practitioners should monitor height and weight parameters relative to age at the initiation of treatment and periodically during therapy.
    Meglitinides: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Meperidine: Amphetamines have been reported to increase the analgesic effects of meperidine. However, due to the MAO-inhibitor activity of amphetamines, the concurrent use amphetamine and meperidine is not recommended. Hypotension, severe respiratory depression, coma, convulsions, hyperpyrexia, vascular collapse, and death can occur.
    Meperidine; Promethazine: Amphetamines have been reported to increase the analgesic effects of meperidine. However, due to the MAO-inhibitor activity of amphetamines, the concurrent use amphetamine and meperidine is not recommended. Hypotension, severe respiratory depression, coma, convulsions, hyperpyrexia, vascular collapse, and death can occur. Amphetamines may pharmacodynamically counteract the sedative properties of promethazine. 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.
    Mephobarbital: Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamine/dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Metaproterenol: 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: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Metformin; Pioglitazone: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Metformin; Repaglinide: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Metformin; Rosiglitazone: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Metformin; Saxagliptin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Metformin; Sitagliptin: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently. Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Methazolamide: Concurrent use of amphetamines and urinary alkalinizers, such as acetazolamide and methazolamide, should be avoided, especially in dextroamphetamine overdose situations. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Methenamine: 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: 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: 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. Theoretically, concurrent use of methylene blue and amphetamines may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and amphetamines increase central serotonin effects. 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 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. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methohexital: 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: 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.
    Methyldopa: 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.
    Methylene Blue: Theoretically, concurrent use of methylene blue and amphetamines may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and amphetamines increase central serotonin effects. 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 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. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methylergonovine: 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.
    Methylphenidate: The stimulant effects of methylphenidate can be additive when used concurrently with most other psychostimulants. In general the use of methylphenidate with the amphetamines would not be recommended, to avoid duplicate therapies. The combination of methylphenidate with amphetamine may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems.
    Methysergide: 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: 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.
    Metoprolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Miglitol: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Milnacipran: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as amphetamines. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. A man developed marked agitation, anxiety, diaphoresis, shivering, tachycardia, tremor, generalized hypertonia, hyperreflexia, 1 to 2 beats of inducible ankle clonus, frequent myoclonic jerking, and tonic spasm of the right side of his orbicularis oris muscle while taking dexamphetamine and venlafaxine. Cessation of both drugs and administration of cyproheptadine led to a stepwise heart rate reduction and complete symptom resolution. Patients receiving SNRIs and amphetamines should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The SNRI and amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Mirtazapine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering mirtazapine with other drugs that have serotonergic properties such as amphetamines. 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. Patients receiving mirtazapine and amphetamines should be monitored for the emergence of serotonin syndrome. Mirtazapine should be discontinued if a patient develops a combination of symptoms suggestive of serotonin syndrome.
    Modafinil: 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: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Molindone: 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: In general, all types of sympathomimetics and psychostimulants 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 even 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.
    Nabilone: 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: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Nebivolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Nebivolol; Valsartan: 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 or the selection of alternative therapeutic agents may be needed. 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Nefazodone: Although unlikely to occur during monotherapy with nefazodone, serotonin syndrome may occur from combining medications that potentiate serotonin activity. Serotonin syndrome, while uncommon, can be serious and consists of symptoms such as mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia, and fever. At high doses, amphetamines can increase serotonin release, as well as act as serotonin-receptor agonists.
    Nicardipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Nicotine: Nicotine use may potentiate the effects of the adrenergic agonists and the ergot alkaloids. If significant changes in nicotine intake occur, the dosages of these drugs may need adjustment.
    Nifedipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Nimodipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Nisoldipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Nitrates: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Non-Ionic Contrast Media: 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: 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.
    Olmesartan: 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 or the selection of alternative therapeutic agents may be needed.
    Ombitasvir; Paritaprevir; Ritonavir: Patients receiving amphetamines may experience prolonged effects if receiving ritonavir concurrently. A case report describes a patient who was treated with ritonavir and saquinavir and then experienced a prolonged effect from a small dose of methylene-dioxy-methamphetamine (MDMA or ecstasy) and a near fatal reaction from a small dose of gamma-hydroxybutyrate (GHB). The effects in this patient suggests that the prolonged effects of MDMA were due to ritonavir-induced inhibition of CYP2D6 metabolism. The GHB toxicity in this patient may have been due to ritonavir-induced inhibition of first pass metabolism, leading to increased levels of GHB. Patients receiving other amphetamine drugs, such as amphetamine, amphetamine; dextroamphetamine mixed salts, lisdexamfetamine, or methamphetamine may experience prolonged effects if receiving ritonavir concurrently. Patients should be warned that there are potentially serious drug interactions between ritonavir and illicit drugs, such as ecstasy.
    Omeprazole; Sodium Bicarbonate: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Oxcarbazepine: 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.
    Paliperidone: 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.
    Paroxetine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Penbutolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Pentobarbital: 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.
    Perampanel: 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.
    Pergolide: 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: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Perindopril; Amlodipine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Phenelzine: In general, all types of sympathomimetics and psychostimulants 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 even 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: 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.
    Phenothiazines: 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.
    Phenoxybenzamine: 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: Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should generally not be used in combination with other sympathomimetics or psychostimulants. Cardiovascular or CNS side effects may increase, and some may be serious. The safety and efficacy of coadministration of phentermine with other products intended for weight loss or ADHD including prescription drugs (e.g., amphetamines) have not been established.
    Phentermine; Topiramate: Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should generally not be used in combination with other sympathomimetics or psychostimulants. Cardiovascular or CNS side effects may increase, and some may be serious. The safety and efficacy of coadministration of phentermine with other products intended for weight loss or ADHD including prescription drugs (e.g., amphetamines) have not been established. Concurrent use of amphetamines and urinary alkalinizers, such as topiramate, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, 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.
    Phentolamine: 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.
    Phenylephrine; Promethazine: Amphetamines may pharmacodynamically counteract the sedative properties of promethazine. 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.
    Phenytoin: Amphetamine or dextroamphetamine may delay the intestinal absorption of orally-administered phenytoin; the extent of phenytoin absorption is not known to be effected. Monitor the patient's neurologic status closely, as the amphetamines may also lower the seizure threshold in some patients on phenytoin or fosphenytoin.
    Pimozide: Pimozide should not be used to treat motor or phonic tics in patients taking drugs that may cause tics such as amphetamines until such patients have been withdrawn from these drugs to determine whether or not the drugs, rather than Tourette's Disorder, are responsible for the tics. In addition, pimozide 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 pimozide, through central dopamine antagonist activity, may diminish the effectiveness of amphetamines.
    Pindolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Pioglitazone: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Pirbuterol: 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 Citrate: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Potassium Salts: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Potassium-sparing diuretics: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Pramlintide: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Prazosin: 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.
    Pregabalin: 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.
    Primidone: 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.
    Procarbazine: 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, phentermine and other drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless absolutely 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 producs, weight loss products, and energy supplements that contain sympathomimetic agents.
    Promethazine: Amphetamines may pharmacodynamically counteract the sedative properties of promethazine. 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.
    Propofol: 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: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Proton pump inhibitors: Patients receiving amphetamine; dextroamphetamine or extended-release amphetamine; dextroamphetamine with a proton pump inhibitor should be monitored for changes in clinical efficacy. Proton pump inhibitors (PPIs) may alter the pharmacokinetics of amphetamine; dextroamphetamine due to a reduction in gastric acidity. An interaction has been noted with the extended-release product (Adderall XR) when administered with a PPI. Co-administration of Adderall XR 20 mg and omeprazole 40 mg resulted in a decrease in median Tmax of d-amphetamine and l-amphetamine by 1.25 hours and 2.5 hours, respectively, compared to administration of Adderall XR alone.The AUC and maximal concentration (Cmax) of each moiety were unaffected.
    Quetiapine: 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.
    Quinapril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Racepinephrine: 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: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Rasagiline: 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.
    Reserpine: 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: Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy if taking riociguat with a sympathomimetic.
    Risperidone: 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.
    Ritonavir: Patients receiving amphetamines may experience prolonged effects if receiving ritonavir concurrently. A case report describes a patient who was treated with ritonavir and saquinavir and then experienced a prolonged effect from a small dose of methylene-dioxy-methamphetamine (MDMA or ecstasy) and a near fatal reaction from a small dose of gamma-hydroxybutyrate (GHB). The effects in this patient suggests that the prolonged effects of MDMA were due to ritonavir-induced inhibition of CYP2D6 metabolism. The GHB toxicity in this patient may have been due to ritonavir-induced inhibition of first pass metabolism, leading to increased levels of GHB. Patients receiving other amphetamine drugs, such as amphetamine, amphetamine; dextroamphetamine mixed salts, lisdexamfetamine, or methamphetamine may experience prolonged effects if receiving ritonavir concurrently. Patients should be warned that there are potentially serious drug interactions between ritonavir and illicit drugs, such as ecstasy.
    Rosiglitazone: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Rufinamide: 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.
    Sacubitril; Valsartan: 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 or the selection of alternative therapeutic agents may be needed.
    Salmeterol: Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Saxagliptin: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Sedating H1-blockers: 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.
    Selective serotonin reuptake inhibitors: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Selegiline, Transdermal: In general, all types of sympathomimetics and psychostimulants 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 even 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.
    Selegiline: In general, all types of sympathomimetics and psychostimulants 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 even 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.
    Selexipag: Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy if taking selexipag with a sympathomimetic.
    Serotonin norepinephrine reuptake inhibitors: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as amphetamines. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. A man developed marked agitation, anxiety, diaphoresis, shivering, tachycardia, tremor, generalized hypertonia, hyperreflexia, 1 to 2 beats of inducible ankle clonus, frequent myoclonic jerking, and tonic spasm of the right side of his orbicularis oris muscle while taking dexamphetamine and venlafaxine. Cessation of both drugs and administration of cyproheptadine led to a stepwise heart rate reduction and complete symptom resolution. Patients receiving SNRIs and amphetamines should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The SNRI and amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Serotonin-Receptor Agonists: Although unlikely to occur during monotherapy with 5-HT1 agonists, serotonin syndrome may occur from combining medications that potentiate serotonin activity. Serotonin syndrome, while uncommon, can be serious and consists of symptoms such as mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia, and fever. At high doses, amphetamines can increase serotonin release, as well as act as serotonin-receptor agonists.
    Sertraline: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with SSRI use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. The safe and effective use of SSRIs with amphetamines has not been established; however, this combination has been used clinically. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and SSRIs. If serotonin syndrome is suspected, concurrent use should be discontinued.
    Sevoflurane: 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.
    Sibutramine: Sibutramine is contraindicated in patients taking other centrally-acting appetite suppressant drugs (e.g., amphetamine, dextroamphetamine). In addition, many of these agents enhance central serotonergic activity by various mechanisms. Concurrent use of sibutramine with other serotonergic agents may increase the potential for serotonin syndrome or neuroleptic malignant syndrome-like reactions. 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.
    Simvastatin; Sitagliptin: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Sitagliptin: Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Sodium Bicarbonate: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Sodium Lactate: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Sodium Oxybate: 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.
    Sotalol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    St. John's Wort, Hypericum perforatum: St. John's wort, Hypericum Perforatum may reduce the neuronal uptake of monoamines and should be used cautiously with sympathomimetics.
    Succinimides: 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.
    Sulfonylureas: Endogenous epinephrine is released in response to hypoglycemia; epinephrine, through stimulation of alpha- and beta- receptors, increases hepatic glucose production and glycogenolysis and inhibits insulin secretion in order to increase serum glucose concentrations. A pharmacodynamic interaction may occur when pseudoephedrine and other sympathomimetics are administered to patients as these agents may increase blood glucose concentrations by a similar mechanism. Patients receiving sulfonylureas should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Fenfluramine and dexfenfluramine may potentiate the actions of some antidiabetic agents via increasing glucose uptake by muscle cells. Monitor patients taking either of these drugs in combination with glyburide for hypoglycemia.
    Tamsulosin: 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.
    Tedizolid: 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: 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 or the selection of alternative therapeutic agents may be needed.
    Terazosin: 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.
    Terbutaline: Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Theophylline, Aminophylline: Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. 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.
    Thiazolidinediones: Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to avoid hypoglycemia, it appears that amphetamines can be used concurrently.
    Thiopental: 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: 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: 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.
    Tiagabine: 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.
    Timolol: 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. Due to the risk of unopposed alpha-adrenergic activity, sympathomimetics should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed.
    Topiramate: Concurrent use of amphetamines and urinary alkalinizers, such as topiramate, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, 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.
    Tramadol: The risk of seizures from the use of tramadol may be increased with concomitant use of CNS stimulants and anorectics that may induce seizures, including the amphetamines. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Trandolapril: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Trandolapril; Verapamil: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin-converting enzyme inhibitors. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Tranylcypromine: In general, all types of sympathomimetics and psychostimulants 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 even 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: Amphetamines may stimulate the release of serotonin in the CNS, and thus may interact with serotonin-enhancing medications such as trazodone. In theory, the rare, but potentially serious, complication of 'serotonin syndrome' could result from this combination (presenting as rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, delirium, 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 serotonin-enhancing medications. Close monitoring is advisable when combination therapy is initiated or dosages are increased.
    Treprostinil: 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.
    Tricyclic antidepressants: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as amphetamines. Both TCAs and amphetamines inhibit the reuptake of serotonin and amphetamines also increase central serotonin release. 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. The MAOI and sympathomimetic activity of amphetamines may also be of concern. The actions of TCAs may be enhanced by concurrent use with amphetamines. For example, levels of dextroamphetamine may be increased within the CNS. Theoretically, the cardiovascular effects of the amphetamines may be potentiated by TCAs through the stimulation of the release of norepinephrine. Although combination therapy with amphetamines and TCAs has been used clinically, further study is needed to fully evaluate the severity and frequency of adverse effects that may occur. If serotonin syndrome is suspected, the agents should be discontinued. If the patient experiences changes in heart rate or rhythm, an ECG may be indicated. Dose reduction of the amphetamine may be needed if side effects occur.
    Tromethamine: Concurrent use of amphetamines with urinary alkalinizing agents (e.g., sodium lactate, sodium acetate, potassium citrate, citric acid; sodium citrate, and tromethamine) should be avoided if possible. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of the amphetamines. The half-life and therapeutic actions of amphetamines will be prolonged. The amphetamine dose should be adjusted accordingly if avoiding co-use is not possible. Monitor for high blood pressure, increased heart rate, nervousness, palpitations, insomnia, or changes in moods and behaviors.
    Umeclidinium; Vilanterol: 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.
    Valproic Acid, Divalproex Sodium: 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, discontinue the amphetamine.
    Valsartan: 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 or the selection of alternative therapeutic agents may be needed.
    Vasodilators: Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Vasopressors: Amphetamines may enhance the activity of other sympathomimetics (e.g., ephedrine, norepinephrine, pseudoephedrine, ephedra alkaloids or Ma huang); cardiovascular or CNS stimulant effects can be potentiated. Increased heart rate, blood pressure, or cardiac arrhythmias can occur in some patients.
    Venlafaxine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as amphetamines. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. A man developed marked agitation, anxiety, diaphoresis, shivering, tachycardia, tremor, generalized hypertonia, hyperreflexia, 1 to 2 beats of inducible ankle clonus, frequent myoclonic jerking, and tonic spasm of the right side of his orbicularis oris muscle while taking dexamphetamine and venlafaxine. Cessation of both drugs and administration of cyproheptadine led to a stepwise heart rate reduction and complete symptom resolution. Patients receiving SNRIs and amphetamines should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The SNRI and amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Verapamil: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as calcium-channel blockers. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Vigabatrin: 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.
    Vilazodone: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with vilazodone use. Patients receiving vilazodone and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and the amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Vortioxetine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as amphetamines. 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. The MAOI activity of amphetamines may also be of concern with vortioxetine use. Monitor for adverse effects, such as anger, irritability, insomnia, and headache when treatments are combined. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and serotonergic. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.
    Yohimbine: At high doses, yohimbine may nonselectively inhibit monoamine oxidase and also, at normal doses, activates the sympathetic nervous system via selective central alpha 2-adrenoceptor antagonism. Traditional MAOIs can cause serious adverse effects when taken concomitantly with sympathomimetics.
    Ziprasidone: Ziprasidone should be used cautiously with drugs that are known to lower seizure threshold such as amphetamine or dextroamphetamine. Also, ziprasidone has a risk for QT prolongation, and amphetamines can potentially sensitize the myocardium.
    Zonisamide: 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 in human breast milk by the lactating mother. According to the manufacturer, it is advisable to avoid breast-feeding during the use of amphetamines. Concentrations in breast-milk are often more concentrated than plasma levels. Breast milk concentrations in one woman taking 20 mg daily of racemic amphetamine ranged from 55 to 138 ng/mL with milk to plasma ratios of 2.8 to 7.5. The infant was monitored for 24 months and no adverse effects from amphetamine exposure were noted. Methylphenidate may be considered an alternative to amphetamine agents in women who are breast-feeding an infant, although the medical use of stimulant medications has not been formally evaluated during lactation. The AAP previously considered amphetamines, when used as drugs of abuse, to be contraindicated in breast-feeding due to concerns of irritability and poor sleeping pattern in the infant. 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. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Amphetamine and dextroamphetamine are non-catecholamine sympathomimetic agents that stimulate the release of norepinephrine (NE) and other biologic amines from central adrenergic receptors. At higher dosages, they cause release of dopamine (DA) from the mesocorticolimbic system and the nigrostriatal dopamine systems. It is thought that the release of dopamine is responsible for the reinforcing properties of amphetamine. At still higher doses, amphetamine stimulates the release of 5-hydroxytryptamine (5-HT). Finally, amphetamine may act as a direct agonist on central 5-HT receptors. Thus, amphetamine is both a direct and an indirect stimulant. Amphetamines may also inhibit monoamine oxidase (MAO), but this is a minor action. Dextroamphetamine exhibits greater CNS stimulation than racemic- or levo- amphetamine on a weight basis. Amphetamine-induced CNS stimulation produces a decreased sense of fatigue, an increase in motor activity and mental alertness, mild euphoria, and brighter spirits. Lithium may offset amphetamine-induced euphoria.
     
    •Peripheral actions: 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. Dextroamphetamine has less peripheral activity than racemic amphetamine at normally prescribed dosages. Amphetamines increase systolic and diastolic blood pressure and cause respiratory stimulation and weak bronchodilation. Heart rate typically increases slightly with normal therapeutic doses of stimulants (about 3—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 may produce mydriasis and contraction of the bladder sphincter.
     
    •Actions in ADHD: 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. Current research suggests that the modulation of serotonergic pathways by the amphetamines may contribute to the calming effects in the treatment of this disorder.
     
    •Anorectic actions: The action of the amphetamines in treating obesity may result from mechanisms besides appetite suppression at the lateral hypothalamic feeding center. It has been suggested that amphetamines decrease olfactory acuity, which may contribute to their anorexic properties. Amphetamines do not seem to alter the basal metabolic rate or nitrogen excretion. It is unknown if other CNS actions or metabolic effects may be involved in the promotion of weight loss with amphetamines.

    PHARMACOKINETICS

    Amphetamine and dextroamphetamine mixed salts are administered orally. Commercially available products (e.g., Adderall and Adderall XR) contain d-amphetamine and l-amphetamine salts in the ratio of 3:1. Amphetamine; dextroamphetamine is widely distributed throughout the body, including the central nervous system (CNS). Volume of distribution (Vd) increases as body weight increases. Amphetamine is reported to be oxidized at the 4 position of the benzene ring to form 4-hydroxyamphetamine, or on the side chain alpha- or beta- carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively. Norephedrine and 4-hydroxy-amphetamine are both active and each is subsequently oxidized to form 4-hydroxy-norephedrine. Alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the glycine conjugate hippuric acid. 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, variations in amphetamine metabolism are a possibility. Children exhibit a higher clearance than adolescents and adults when adjusted for body weight. Under normal conditions, the plasma half-life of amphetamine; dextroamphetamine mixed salts is roughly 9—11 hours in children >= 6 years, 11—14 hours in adolescents, and 10—13 hours in adults.
     
    Amphetamines and their metabolites are excreted in the urine. With normal urine pH, approximately 30—40% of the administered dose is recoverable in urine as amphetamine and 50% as alpha-hydroxy-amphetamine (inactive metabolite). Since amphetamine has a pKa of 9.9, urinary recovery of amphetamine is highly dependent on pH and urine flow rates. Alkaline urine pHs result in less ionization and reduced renal elimination of amphetamine. Conversely, acidification of the urine and high urinary flow rates result in increased renal elimination with clearances greater than glomerular filtration rates, indicating the involvement of active secretion. Urinary recovery of amphetamine has be reported to range from 1—75% depending on urinary pH. The urinary elimination of amphetamines and their metabolites may be affected by agents that acidify or alkalinize the urinary fluids.

    Oral Route

    Following oral administration, the onset of action occurs within 30—60 minutes. Maximum systemic absorption of Adderall tablets is completed within 3 hours, and within 7 hours for Adderall XR capsules. A single dose of Adderall XR 20 mg gives comparable plasma concentrations to Adderall tablets given in a 10 mg bid dosage. Sprinkling Adderall XR on applesauce gives comparable plasma concentrations to administration in the fasted state. Otherwise, if given with more food, absorption is not affected but the Tmax is prolonged by roughly 2.5 hours. Pharmacokinetic parameters are linear over the normal dosage range.
    Amphetamine and dextroamphetamine are widely distributed throughout the body, including the CNS. Therapeutic response has been correlated with amphetamine serum concentrations of 5—10 mcg/dL.