PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Narcolepsy Agents
    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 disease, ventricular arrhythmias, ventricular dysfunction

    Dextroamphetamine is contraindicated in patients with moderate to severe hypertension, advanced arteriosclerosis, or symptomatic cardiac disease. 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, but 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

    Oral CNS stimulant; is the dextro-isomer of racemic amphetamine and twice as potent
    Used for narcolepsy and as an adjunct in the treatment of attention-deficit disorder
    Many states in the US restrict use as an anorectic agent

    COMMON BRAND NAMES

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

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For the treatment of attention-deficit hyperactivity disorder (ADHD).
    NOTE: 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. Stimulants have been shown to be effective first-line agents in the treatment of ADHD.
    NOTE: Avoid late evening doses to help prevent insomnia. Reduce dose if anorexia or insomnia occur.
    Oral dosage (tablets or solution)
    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 the daily dose by no more than 5 mg/week; dosage above 40 mg/day PO is not usually necessary. Dosage should be individualized based upon response and tolerability; use the lowest effective dose after stabilization. Stimulants are agents of choice in the management of ADHD in adults.

    Children and Adolescents 6 years and older

    Initially, 5 mg PO once or twice daily. May titrate daily dose in 5 mg increments at weekly intervals to minimum effective dose. Daily dose may be given in 1 to 3 divided doses at 4 to 6 hour intervals. Max: 40 mg/day. Only in rare cases will it be necessary to exceed a total of 40 mg/day PO. Some experts recommend a maximum dose of 60 mg/day in patients weighing more than 50 kg.

    Children 3 to 5 years

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

    Oral dosage (extended-release capsules)
    Adults†

    5 mg PO once or twice daily initially; then, may increase by 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg/day PO. The extended-release capsules may be used for once-a-day dosage wherever appropriate. Dosage should be individualized based upon response and tolerability; use the lowest effective dose after stabilization. Stimulants are agents of choice in the management of ADHD in adults.

    Children and Adolescents 6 years and older

    Initially, 5 mg PO once or twice daily. May titrate by 5 mg increments at weekly intervals to a minimum effective dose. Twice daily dosing should be given with an interval of approximately 8 hours; avoid late evening administration. A dosage more than 40 mg/day is rarely necessary; however, some experts recommend a maximum dose of 60 mg/day in patients weighing more than 50 kg. The extended-release capsules may be used for once-a-day dosage wherever appropriate.

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

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

    Children 6 to 11 years

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

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

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

    Children 6 to 11 years

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

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

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

    Oral dosage (extended-release capsule)
    Adults

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

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

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

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    60 mg/day PO.

    Geriatric

    60 mg/day PO; individualize dosage based on response and tolerability.

    Adolescents

    60 mg/day PO.

    Children

    6 years and older: 60 mg/day PO.
    3 to 5 years: Maximum dosage information is not provided in the FDA-approved labeling; doses should not exceed 40 mg/day PO for immediate-release formulations. Do not use extended-release formulations.
    Less than 3 years: Safety and efficacy have not been established.

    Infants

    Not indicated.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

     
    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

    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 interference with sleep.
    When used as an anorectic, give dose 30—60 minutes before meals.

    Oral Solid Formulations

    Instruct patient not to crush or chew the extended-release capsules.

    Oral Liquid Formulations

    Administer oral solution using a calibrated measuring device.

    STORAGE

    Dexedrine:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Dexedrine Spansule:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    DextroStat:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Liquadd :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    ProCentra :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in original container
    Zenzedi:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

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

    Alcoholism, substance abuse

    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). Dextroamphetamine has 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

    Dextroamphetamine is contraindicated in patients in an agitated state. Stimulants such as dextroamphetamine should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur. An assessment should be performed prior to initiation of therapy to determine the risk for bipolar disorder in patients presenting with symptoms of depression. Due to its toxic effects in overdose, dextroamphetamine should only be used in those with major depression or suicidal ideation when absolutely necessary. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and 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

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

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

    Dextroamphetamine is contraindicated in patients with moderate to severe hypertension, advanced arteriosclerosis, or symptomatic cardiac disease. 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, but 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 at usual doses for ADHD ; therefore, patients with cerebrovascular disease should be closely monitored. Stimulant medications may increase blood pressure or heart rate in some individuals.

    Glaucoma, visual disturbance

    Dextroamphetamine is contraindicated in patients with glaucoma, due to the ability of sympathetic stimulation to block aqueous outflow and raise intraocular pressure. Occasionally, visual disturbance, such as change in visual accomodation or blurred vision, have been reported in individuals without ocular disease while they are taking dextroamphetamine. Patients should report any new visual disturbance as ophthalmic evaluation may be needed.

    Hyperthyroidism, thyrotoxicosis

    Dextroamphetamine is contraindicated for use in thyroid disease patients with hyperthyroidism, including thyrotoxicosis, as sympathomimetic stimulation may induce cardiac arrhythmias or other side effects.

    Neonates, pregnancy

    Dextroamphetamine is classified as FDA pregnancy risk category C. There are no adequate and well controlled studies of dextroamphetamine use in pregnant women. Dextroamphetamine should only be used during pregnancy if the expected benefit to the mother clearly outweighs the potential fetal risk. Amphetamines have been shown to have both embryotoxic and teratogenic effects in some animals when administered at high doses. 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 are known to occur in human neonates who are born to mothers dependent on amphetamines. These have included increased incidences of premature births, low birth weights and length, lower occipitofrontal circumference, and physical withdrawal symptoms (e.g., abnormal sleep patterns, poor feeding, tremor, agitation, fatigue, and hypertonia). In one prospective comparison study, neonates exposed to cocaine, methamphetamine, or a combination of cocaine and narcotic in utero had a 35.1% incidence of cranial abnormalities (i.e., intraventricular hemorrhage, echodensities known to be associated with necrosis, and cavitary lesions) compared to a 5.3% incidence in normal infants as assessed by cranial ultrasonography. The authors speculated that the ultrasonographic abnormalities were probably related to the vasoconstrictive properties of the drugs. The effects of dextroamphetamine during labor and delivery are unknown.

    Breast-feeding

    According to the manufacturer, amphetamines are excreted into breast milk, and women who are taking amphetamines should refrain from breast-feeding. The effect of stimulant medication exposure via breast milk on the neurological development of the infant has not been well studied. 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. Similarly, there were no reports of neonatal insomnia or stimulation in 103 nursing infants whose mothers were taking various amounts of amphetamine. In one study of 4 women with attention deficit hyperactivity disorder receiving d-amphetamine (median dose 18 mg/day) while breast-feeding, the mean relative infant dose was 5.7% of the weight-adjusted maternal dose (range: 3.9 to 13.8%). Of the 3 infants in whom blood samples were obtained, plasma d-amphetamine levels were undetectable in one; d-amphetamine levels were approximately 6% and 14% of the corresponding maternal plasma concentrations in the remaining two infants. None of the four infants in the study showed any adverse effects. 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. If possible, long-term infant exposure to stimulants through breast milk should be avoided since the consequences of such exposure are unknown. 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.

    Tics, Tourette's syndrome

    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 and at the lowest effective dose.

    Driving or operating machinery

    The use of 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 dextroamphetamine with caution in patients with seizures or a history of a seizure disorder because the seizure threshold can be reduced, particularly during excess CNS stimulation (i.e., amphetamine overdosage). The effects of amphetamines on the seizure threshold, in normal therapeutic dosages, are less clear. Seizure threshold may be reduced in those with EEG abnormalities and rarely in patients without a seizure history or EEG abnormalities. If seizures occur, discontinuation of therapy is recommended.

    Surgery

    The use of inhalational anesthetics during surgery may sensitize the myocardium to the effects of dextroamphetamine.

    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. Dextroamphetamine 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 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.

    Hypercortisolism

    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 dextroamphetamine if determination of plasma corticosteroid concentrations is desired.

    Geriatric

    Dextroamphetamine should be used with caution in the geriatric patient for the treatment of attention deficit disorder (ADD/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.

    Hepatic disease, renal impairment

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

    Children, growth inhibition, infants

    Children 3 years and older have been successfully treated for attention-deficit hyperactivity disorder (ADHD) with amphetamines. Safety and efficacy of dextroamphetamine have not been established in infants and children less than 3 years old. Sustained-release dextroamphetamine is not recommended for children less than 6 years of age. Amphetamines in general are not used for the management of obesity in children under 12 years of age. It should be noted that not all children with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy. 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; 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. It 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—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. Data are inadequate to determine whether chronic use of stimulants causes long-term growth inhibition. Although data are limited, available studies do not indicate that stimulant use compromises the attainment of normal adult height and weight in most children. 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—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).

    MAOI therapy

    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 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

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

    Moderate

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

    Mild

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

    DRUG INTERACTIONS

    Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Acebutolol: (Major) 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: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Acetaminophen; Tramadol: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as tramadol. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and tramadol. Patients receiving tramadol and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and tramadol should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, the risk of seizures from the use of tramadol may be increased with concomitant use of CNS stimulants that may induce seizures, including the amphetamines. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Acetazolamide: (Major) 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: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Albuterol: (Major) 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: (Major) 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: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Aliskiren; Amlodipine: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Aliskiren; Valsartan: (Major) 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: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Alogliptin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Alpha-glucosidase Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Aluminum Hydroxide: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Moderate) Careful observation is required when amantadine is administered concurrently with central nervous system (CNS) stimulants. An increase in stimulant effects, such as nervousness, irritability, insomnia, tremor, seizures, or cardiac arrhythmias may occur.
    Ambrisentan: (Major) 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.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with amphetamines and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Amphetamines may increase the risk of seizures.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine: (Major) 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: (Major) 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: (Major) 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. (Major) 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: (Major) 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. (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Major) 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. (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amlodipine; Olmesartan: (Major) 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. (Major) 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: (Major) 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. (Major) 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: (Major) 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. (Major) 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: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Amoxapine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of indirect-acting sympathomimetics, such as amphetamine, however, the data are not consistent.
    Angiotensin II receptor antagonists: (Major) 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: (Major) 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: (Major) 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: (Moderate) Caution and close observation should be used when arformoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Aripiprazole: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Armodafinil: (Major) 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: (Moderate) 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: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Atenolol: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Atomoxetine: (Major) 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: (Severe) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Azilsartan: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Benazepril: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Bendroflumethiazide; Nadolol: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Beta-blockers: (Major) 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: (Major) 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: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
    Bisoprolol: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Bosentan: (Major) Avoid use of sympathomimetic agents with bosentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including bosentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Brimonidine; Timolol: (Major) 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: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
    Budesonide; Formoterol: (Moderate) 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: (Major) 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: (Major) 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.
    Buspirone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as buspirone. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and buspirone. Patients receiving buspirone and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and buspirone should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Cabergoline: (Minor) 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: (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants. Patients may need to reduce, limit, or avoid caffeine intake. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Caffeine; Ergotamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable. (Moderate) Avoid excessive caffeine intake during use of the amphetamine salts. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Calcium Carbonate: (Major) 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: (Major) 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. (Major) 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: (Major) 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; Simethicone: (Major) 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: (Major) 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: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Canagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Candesartan: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Captopril: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Carbamazepine: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Chlorthalidone: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Chlorthalidone; Clonidine: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Chondroitin; Glucosamine: (Moderate) 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.
    Cimetidine: (Moderate) The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration (Tmax) of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed.
    Cinacalcet: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as cinacalcet. Patients should be warned that there are potentially serious drug interactions between cinacalcet and prescription amphetamine therapy or illicit amphetamine use. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented. A case report describes a patient who was treated with another potent CYP2D6 inhibitor 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). Inhibition of CYP2D6 metabolism may have contributed to the resulting toxicity observed in this case.
    Citalopram: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as amphetamines and citalopram. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. Patients receiving citalopram and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. All serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Citric Acid; Potassium Citrate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Citric Acid; Sodium Citrate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Clevidipine: (Major) 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: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. 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: (Major) 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: (Major) 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: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Cocaine: (Severe) Additive effects and increased toxicity may be observed when using cocaine in combination with other sympathomimetics. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as CNS stimulation, hypertensive crisis, cardiac arrhythmias or ischemia (angina).
    Codeine; Phenylephrine; Promethazine: (Major) 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: (Major) 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: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Collagenase: (Moderate) 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.: (Moderate) 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.
    Dacomitinib: (Major) The risk of amphetamine toxicity, including serotonin syndrome, may be increased during concurrent use with dacomitinib. Amphetamines are partially metabolized by CYP2D6; dacomitinib is a strong CYP2D6 inhibitor. Concurrent use may increase exposure to the amphetamine increasing the risk for serotonin syndrome. 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. If serotonin syndrome occurs, both the amphetamine and dacomitinib should be discontinued and appropriate medical treatment should be implemented. Patients should be warned that there are potentially serious drug interactions between dacomitinib and prescription amphetamine therapy or illicit amphetamine use.
    Dapagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as ritonavir. 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). Inhibition of CYP2D6 metabolism by ritonavir may have contributed to the resulting toxicity observed in this case. Because amphetamines are partially metabolized by CYP2D6 and have serotonergic properties, concurrent use with ritonavir may also increase the risk of serotonin syndrome. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented. Patients should be warned that there are potentially serious drug interactions between ritonavir and prescription amphetamine therapy or illicit amphetamine use.
    Delavirdine: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as delavirdine. Patients should be warned that there are potentially serious drug interactions between delavirdine and prescription amphetamine therapy or illicit amphetamine use. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented. A case report describes a patient who was treated with another potent CYP2D6 inhibitor 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). Inhibition of CYP2D6 metabolism may have contributed to the resulting toxicity observed in this case.
    Desvenlafaxine: (Major) 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: (Severe) Amphetamines and dexmethylphenidate should not be coadministered. These drugs represent duplicate treatments for certain conditions. Nervousness, irritability, insomnia, palpitations, arrhythmias, seizures, or other serious stimulant-related adverse effects may occur.
    Dextromethorphan; Promethazine: (Major) 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.
    Dextromethorphan; Quinidine: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as quinidine. Patients should be warned that there are potentially serious drug interactions between quinidine and prescription amphetamine therapy or illicit amphetamine use. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.A case report describes a patient who was treated with another potent CYP2D6 inhibitor 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). Inhibition of CYP2D6 metabolism may have contributed to the resulting toxicity observed in this case.
    Diazepam: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Digitoxin: (Major) 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: (Major) 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: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Diltiazem: (Major) 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.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dorzolamide; Timolol: (Major) 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: (Major) 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: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
    Dulaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Duloxetine: (Major) 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: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Dyphylline: (Major) 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: (Major) 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: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Enalapril, Enalaprilat: (Major) 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: (Major) 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. (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Enflurane: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Eplerenone: (Major) 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: (Major) Avoid use of sympathomimetic agents with epoprostenol. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including epoprostenol. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Eprosartan: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Ergoloid Mesylates: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ergonovine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ergot alkaloids: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ergotamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Ertugliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Ertugliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Escitalopram: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as amphetamines and escitalopram. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. Patients receiving escitalopram and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. All serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Eslicarbazepine: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. 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: (Major) 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: (Major) Alcohol should not be consumerd with some dosage forms (e.g., Mydayis extended-release capsules) of amphetamine/dextroamphetamine salts. Consumption of alcohol while taking such dosage forms may result in a more rapid release of the dose of mixed amphetamine salts. Such effects may potentially lead to serious side effects such as acute anxiety, problems with sleep, or increases in heart rate or blood pressure that may lead to heart problems or stroke.Also, the use of amphetamine/dextroamphetamine salts may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicles; the patient should therefore be cautioned accordingly.
    Ethotoin: (Major) 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: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Exenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Ezogabine: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. 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.
    Famotidine: (Moderate) The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration (Tmax) of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed.
    Famotidine; Ibuprofen: (Moderate) The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration (Tmax) of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed.
    Felbamate: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Felodipine: (Major) 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.
    Fentanyl: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as fentanyl. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and fentanyl. Patients receiving fentanyl and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and fentanyl should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Fluoxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as fluoxetine and 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 the use of drugs that have serotonergic activity. All serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, amphetamines and amphetamine derivatives are metabolized to some degree by CYP2D6 and a kinetic interaction is possible with strong CYP2D6 inhibitors, such as fluoxetine. Increased systemic exposure to amphetamines from CYP2D6 inhibition may result in high blood pressure, tachycardia, anxiety, irritability, insomnia, or other amphetamine-related adverse effects. Patients receiving fluoxetine and an amphetamine should be monitored for the emergence of serotonin syndrome or other adverse effects, particularly during treatment initiation and during dosage increases.
    Fluoxetine; Olanzapine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as fluoxetine and 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 the use of drugs that have serotonergic activity. All serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, amphetamines and amphetamine derivatives are metabolized to some degree by CYP2D6 and a kinetic interaction is possible with strong CYP2D6 inhibitors, such as fluoxetine. Increased systemic exposure to amphetamines from CYP2D6 inhibition may result in high blood pressure, tachycardia, anxiety, irritability, insomnia, or other amphetamine-related adverse effects. Patients receiving fluoxetine and an amphetamine should be monitored for the emergence of serotonin syndrome or other adverse effects, particularly during treatment initiation and during dosage increases. (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Fluticasone; Salmeterol: (Moderate) 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; Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Fluticasone; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Fluvoxamine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as fluvoxamine and 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. Patients receiving fluvoxamine and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. All serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Food: (Major) 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. (Moderate) In general, food does not significantly interact with the amphetamine stimulants, a dose may be taken with or without food. However, certain gastrointestinal acidifying agents (e.g., certain fruit juices, etc.) can lower the oral absorption of amphetamines. To ensure proper absorption, it may be prudent for the patient to avoid citrus fruits and citrus juices 1 hour before a dose, at the time of dosing, and for the 1 hour following a dose. In addition, the excretion of amphetamines is increased in acidic urine and decreased in alkaline urine. Foods that acidify the urine, such as cranberry juice, orange juice, or those that contain vitamin C (ascorbic acid) may increase amphetamine renal excretion. Conversely, foods that alkalinize the urine, such as beets, dairy products, kale, spinach may slightly slow urinary excretion of amphetamines. Patients should not significantly alter their diets, however, as these changes in urinary pH from foods are not expected to be clinically significant for most patients. (Minor) In general, food does not significantly interact with the amphetamine stimulants, a dose may be taken with or without food. Foods that alkalinize the urine, such as beets, dairy products, kale, spinach may slightly slow urinary excretion of amphetamines. Patients should not significantly alter their diets, however, as these alkaline changes in urinary pH from foods are not expected to be clinically significant for most patients.
    Formoterol: (Moderate) 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: (Moderate) 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: (Major) 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: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Fosphenytoin: (Major) 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: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, discontinue use of amphetamines.
    Glimepiride; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glimepiride; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glipizide; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glyburide; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glycopyrrolate; Formoterol: (Moderate) 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: (Major) Some green tea products contain caffeine. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants; caffeine should be avoided or used cautiously.
    Guanabenz: (Major) Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Patients should be monitored for loss of blood pressure control.
    Guanfacine: (Moderate) Sympathomimetic agents, such as amphetamines, may increase blood pressure and reduce the antihypertensive effects of antihypertensive agents, such as guanfacine. Monitor blood pressure and heart rate periodically when prescribed together. Guanfacine may be used adjunctively to psycostimulants such as amphetamines in the treatment of attention deficit hyperactivity disorder (ADHD). Pharmacokinetic studies reveal that guanfacine does not influence lisdexamfetamine pharmacokinetics and lisdexamfetamine does not affect guanfacine pharmacokinetics. No dosage adjustments are required when guanfacine and amphetamines are used together. Monitor heart rate, blood pressure and for sedation during ADHD treatment.
    Guarana: (Major) 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.
    H2-blockers: (Moderate) The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration (Tmax) of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed.
    Haloperidol: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Halothane: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Hydantoins: (Major) 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: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Losartan: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Moexipril: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Propranolol: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Quinapril: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hydrochlorothiazide, HCTZ; Valsartan: (Major) 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. (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Severe) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Ibritumomab Tiuxetan: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Iloperidone: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Iloprost: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Incretin Mimetics: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indapamide: (Moderate) Indapamide may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics and related drugs like indapamide may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate.
    Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulins: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Irbesartan: (Major) 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: (Severe) 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: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Isradipine: (Major) 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: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Labetalol: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Levobetaxolol: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Linagliptin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Linezolid: (Severe) Amphetamines should not be administered during or within 14 days after the use of linezolid. Linezolid possesses MAO-inhibiting activity and can prolong and intensify the cardiac stimulation and vasopressor effects of the amphetamines, potentially resulting in hypertensive crisis. Linezolid also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. If serotonin syndrome occurs, discontinue serotonergic drugs and institute appropriate medical management.
    Liothyronine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Lisinopril: (Major) 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: (Major) The concomitant use of amphetamines and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase of the amphetamine. If serotonin syndrome occurs, discontinue the amphetamine and the concomitant serotonergic drug(s). Examples of serotonergic drugs include lithium.
    Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Loop diuretics: (Major) 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: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as ritonavir. 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). Inhibition of CYP2D6 metabolism by ritonavir may have contributed to the resulting toxicity observed in this case. Because amphetamines are partially metabolized by CYP2D6 and have serotonergic properties, concurrent use with ritonavir may also increase the risk of serotonin syndrome. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented. Patients should be warned that there are potentially serious drug interactions between ritonavir and prescription amphetamine therapy or illicit amphetamine use.
    Lorazepam: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Lorcaserin: (Major) 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: (Major) 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: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Lurasidone: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Magnesium Hydroxide: (Major) 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: (Major) Sympathomimetics may interact with maprotiline, resulting in severe cardiovascular effects including arrhythmias, severe hypertension, hyperpyrexia, and/or severe headaches.
    Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Meperidine: (Major) 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: (Major) 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. (Major) 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: (Major) 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: (Major) Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Repaglinide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Sitagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Methazolamide: (Major) 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: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methenamine; Sodium Acid Phosphate: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Severe) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methohexital: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Methyclothiazide: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Methyldopa: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Methylene Blue: (Severe) Amphetamines should not be administered during or within 14 days after the use of methylene blue. Methylene blue is a potent, reversible monoamine oxidase inhibitor (MAOI) which can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines, potentially resulting in hypertensive crisis. Methylene blue also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents, such as amphetamines, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma.
    Methylergonovine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Methylphenidate: (Severe) Amphetamines and methylphenidate should not be coadministered. These drugs represent duplicate treatments for certain conditions. Nervousness, irritability, insomnia, palpitations, arrhythmias, seizures, or other serious stimulant-related adverse effects may occur.
    Methysergide: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Metolazone: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Metoprolol: (Major) 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: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Milnacipran: (Major) 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: (Moderate) 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: (Major) 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: (Major) 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: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Monoamine oxidase inhibitors: (Severe) 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: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
    Nadolol: (Major) 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: (Major) 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: (Major) 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. (Major) 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: (Moderate) 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: (Major) 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: (Moderate) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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.
    Nizatidine: (Moderate) The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration (Tmax) of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed.
    Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amphetamines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Olanzapine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Olmesartan: (Major) 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: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as ritonavir. 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). Inhibition of CYP2D6 metabolism by ritonavir may have contributed to the resulting toxicity observed in this case. Because amphetamines are partially metabolized by CYP2D6 and have serotonergic properties, concurrent use with ritonavir may also increase the risk of serotonin syndrome. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented. Patients should be warned that there are potentially serious drug interactions between ritonavir and prescription amphetamine therapy or illicit amphetamine use.
    Omeprazole; Sodium Bicarbonate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Paliperidone: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Paroxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as paroxetine and 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 the use of drugs that have serotonergic activity. All serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, amphetamines and amphetamine derivatives are metabolized to some degree by CYP2D6 and a kinetic interaction is possible with strong CYP2D6 inhibitors, such as paroxetine. Increased systemic exposure to amphetamines from CYP2D6 inhibition may result in high blood pressure, tachycardia, anxiety, irritability, insomnia, or other amphetamine-related adverse effects. Patients receiving paroxetine and an amphetamine should be monitored for the emergence of serotonin syndrome or other adverse effects, particularly during treatment initiation and during dosage increases.
    Penbutolol: (Major) 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: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Perampanel: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. 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: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
    Perindopril: (Major) 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: (Major) 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. (Major) 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: (Severe) 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: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use dextroamphetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Phenothiazines: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Phenoxybenzamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Phentermine: (Severe) 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: (Severe) 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. (Major) 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: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Phenylephrine; Promethazine: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Pirbuterol: (Moderate) Caution and close observation should also be used when pirbuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Potassium Bicarbonate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Potassium Citrate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Potassium-sparing diuretics: (Major) 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: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Prazosin: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Pregabalin: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. 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: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures.
    Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Promethazine: (Major) 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: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Propranolol: (Major) 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: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    Quetiapine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Quinapril: (Major) 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.
    Quinidine: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as quinidine. Patients should be warned that there are potentially serious drug interactions between quinidine and prescription amphetamine therapy or illicit amphetamine use. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.A case report describes a patient who was treated with another potent CYP2D6 inhibitor 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). Inhibition of CYP2D6 metabolism may have contributed to the resulting toxicity observed in this case.
    Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using racepinephrine inhalation are advised to avoid other non-prescription products containing sympathomimetics since additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate or blood pressure may be additive. Patients should avoid use of non-prescription decongestants, such as phenylephrine and pseudoephedrine, while using racepinephrine inhalations. Patients should avoid dietary supplements containing ingredients that are reported or claimed to have a stimulant or weight-loss effect, such as ephedrine and ephedra, Ma huang, and phenylpropanolamine. Patients taking prescription sympathomimetic or stimulant medications (including amphetamines, methylphenidate, dexmethylphenidate, isometheptane, epinephrine) should seek health care professional advice prior to the use of racepinephrine inhalations; consider therapeutic alternatives to racepinephrine for these patients.
    Ramipril: (Major) 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.
    Ranitidine: (Moderate) The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration (Tmax) of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed.
    Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.
    Reserpine: (Major) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as reserpine, lowers the absorption of amphetamines, reducing their efficacy. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure such as reserpine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Risperidone: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Ritonavir: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as ritonavir. 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). Inhibition of CYP2D6 metabolism by ritonavir may have contributed to the resulting toxicity observed in this case. Because amphetamines are partially metabolized by CYP2D6 and have serotonergic properties, concurrent use with ritonavir may also increase the risk of serotonin syndrome. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented. Patients should be warned that there are potentially serious drug interactions between ritonavir and prescription amphetamine therapy or illicit amphetamine use.
    Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Rufinamide: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. 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: (Major) 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.
    Safinamide: (Severe) Safinamide is contraindicated for use with Amphetamines due to the risk of serotonin syndrome. 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.
    Salmeterol: (Moderate) 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.
    Sedating H1-blockers: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
    Selegiline: (Severe) 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: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Semaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Serotonin norepinephrine reuptake inhibitors: (Major) 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: (Major) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. 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 agonists. Although unlikely to occur during monotherapy with serotonin-receptor agonists (or "triptans"), serotonin syndrome may occur from combining these drugs with other medications that potentiate serotonin activity. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Sertraline: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as amphetamines and sertraline. 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. In addition, the MAOI activity of amphetamines may be of concern with the use of drugs that have serotonergic activity. Patients receiving sertraline and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. All serotonergic agents should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Sevoflurane: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    SGLT2 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Sibutramine: (Severe) Sibutramine is contraindicated in patients taking other centrally-acting appetite suppressant drugs (e.g., amphetamines). Consider alternatives. Concurrent use of sibutramine with amphetamines can raise blood pressure and heart rate. Use of sibutramine with other serotonergic agents, such as the amphetamines, also increases the risk for serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Discontinue treatment with the amphetamine and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment.
    Sodium Bicarbonate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Sodium Lactate: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Sodium Oxybate: (Moderate) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with psychostimulants that are known to lower seizure threshold such as the amphetamines. Note that CNS stimulants, including the amphetamines, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
    Sotalol: (Major) 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: (Major) St. John's wort, Hypericum Perforatum may reduce the neuronal uptake of monoamines and should be used cautiously with sympathomimetics.
    Succinimides: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. 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: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Tamsulosin: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Tedizolid: (Minor) Theoretically, drugs that possess MAO-inhibiting activity, such as tedizolid, can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid, which is structurally similar to tedizolid, and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including amphetamines.
    Telmisartan: (Major) 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: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Terbutaline: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. Seizures or cardiac arrhythmias are also possible.
    Thiazide diuretics: (Moderate) Thiazides may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate. Amphetamines increase both systolic and diastolic blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Thiazolidinediones: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Thiopental: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Thiothixene: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Thyroid hormones: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Tiagabine: (Major) 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: (Major) 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.
    Tipranavir: (Major) The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as tipranavir. Patients should be warned that there are potentially serious drug interactions between tipranavir and prescription amphetamine therapy or illicit amphetamine use. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. 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. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented. A case report describes a patient who was treated with another potent CYP2D6 inhibitor 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). Inhibition of CYP2D6 metabolism may have contributed to the resulting toxicity observed in this case.
    Topiramate: (Major) 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: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as tramadol. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and tramadol. Patients receiving tramadol and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and tramadol should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. In addition, the risk of seizures from the use of tramadol may be increased with concomitant use of CNS stimulants that may induce seizures, including the amphetamines. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Trandolapril: (Major) 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: (Major) 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. (Major) 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: (Severe) 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: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering trazodone 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 trazodone. The safe and effective use of trazodone 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 trazodone. Patients receiving trazodone and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Trazodone and the amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Tricyclic antidepressants: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as amphetamines and tricyclic antidepressants (TCAs). Both TCAs and amphetamines inhibit the reuptake of serotonin and amphetamines also increase central serotonin release. 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 and sympathomimetic activity of amphetamines may also be of concern. Theoretically, the cardiovascular effects of TCAs or amphetamines may be potentiated through the stimulation of norepinephrine release. Although combination therapy with amphetamines and TCAs is used clinically, further study is needed to fully evaluate the severity and frequency of adverse effects that may occur. If serotonin syndrome is suspected, all serotonergic agents should be discontinued and appropriate medical management should be initiated. If the patient experiences changes in heart rate or rhythm, an ECG may be indicated. A dose reduction of one or both agents may be needed if side effects occur.
    Tromethamine: (Major) Concurrent use of amphetamines with urinary alkalinizing agents should be avoided if possible. If avoidance is not possible, the dose of the amphetamine therapy may need to be adjusted (decreased) in some patients. Monitor for increased blood pressure, increased heart rate, decreased appetite, palpitations, insomnia, irritability, anxiety, or other changes in moods and behaviors. 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.
    Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Valproic Acid, Divalproex Sodium: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, discontinue the amphetamine.
    Valsartan: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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. The MAOI activity of amphetamines may also be of concern with vortioxetine use. Patients receiving vortioxetine and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vortioxetine and the amphetamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Yohimbine: (Major) 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: (Major) 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: (Major) 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

    According to the manufacturer, amphetamines are excreted into breast milk, and women who are taking amphetamines should refrain from breast-feeding. The effect of stimulant medication exposure via breast milk on the neurological development of the infant has not been well studied. 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. Similarly, there were no reports of neonatal insomnia or stimulation in 103 nursing infants whose mothers were taking various amounts of amphetamine. In one study of 4 women with attention deficit hyperactivity disorder receiving d-amphetamine (median dose 18 mg/day) while breast-feeding, the mean relative infant dose was 5.7% of the weight-adjusted maternal dose (range: 3.9 to 13.8%). Of the 3 infants in whom blood samples were obtained, plasma d-amphetamine levels were undetectable in one; d-amphetamine levels were approximately 6% and 14% of the corresponding maternal plasma concentrations in the remaining two infants. None of the four infants in the study showed any adverse effects. 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. If possible, long-term infant exposure to stimulants through breast milk should be avoided since the consequences of such exposure are unknown. 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

    The predominant mechanism of dextroamphetamine's CNS effects is to stimulate the release of several biogenic amines from storage sites in the nerve terminal. Each molecule of amphetamine that is taken up by the nerve terminal displaces one molecule of neurotransmitter. At typical doses, amphetamines stimulate the release of norepinephrine. At higher doses, dopamine is released from its storage sites accounting for some of the behavioral changes seen with amphetamine. 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). It is this neurotransmitter that is thought to explain the overt psychotic behavior associated with amphetamine excess. Finally, amphetamine may act as a direct agonist on central 5-HT receptors. Thus, amphetamine is both a direct and an indirect stimulant. Indirect agonists are associated with tachyphylaxis due to the ever-decreasing supply of endogenous neurotransmitter than can be displaced from the nerve ending. Amphetamines may also inhibit monoamine oxidase (MAO), but this is a minor action. The primary sites of activity in the CNS appear to be in the cerebral cortex and the reticular activating system. Amphetamine-induced CNS stimulation produces a decreased sense of fatigue, an increase in motor activity and mental alertness, mild euphoria, and brighter spirits. These effects are believed to be due to stimulation of norepinephrine release from central noradrenergic neurons. Lithium may offset amphetamine-induced euphoria. Of the two isomers of amphetamine, dextroamphetamine appears to have greater CNS stimulation.
     
    •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

    Dextroamphetamine is administered orally. Distribution is to most body tissues with high concentrations found in the CNS. Metabolism occurs in the liver and excretion is via the kidney. Under normal physiologic conditions the plasma half-life is 10 to 12 hours in adults. The urinary elimination of amphetamines may be affected by agents that acidify or alkalinize the urinary fluids. In general, for every 1 unit increase in urinary pH, there is a reported 7-hour increase in amphetamine half-life. Conversely, acidification of the urine speeds amphetamine elimination.

    Oral Route

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