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  • CLASSES

    Centrally-Acting Antiobesity Agents

    DEA CLASS

    Rx, schedule III

    DESCRIPTION

    Oral, indirect-acting sympathomimetic amine; metabolized to amphetamine and methamphetamine
    Used as an anorectic agent in the short-term (8 to 12 weeks) exogenous treatment of obesity
    Potential for abuse and addiction; not generally recommended by guidelines due to lack of longer-term health benefits

    COMMON BRAND NAMES

    Didrex, Regimex

    HOW SUPPLIED

    Benzphetamine/Benzphetamine Hydrochloride/Didrex/Regimex Oral Tab: 25mg, 50mg

    DOSAGE & INDICATIONS

    For the short-term (i.e., 8 to 12 weeks) treatment of exogenous obesity.
    Oral dosage
    Adults

    Initially, 25 to 50 mg PO once daily, preferably at mid-morning or mid-afternoon. Increase according to patient response, up to 50 mg PO 3 times daily. Max: 150 mg/day PO. Continue only if the patient has satisfactory weight loss within the first 4 weeks of treatment (i.e., weight loss of at least 4 pounds, or as determined by the physician). When tolerance to the anorectic effect develops, do not exceed the recommended dose in an attempt to increase the effect; instead, the drug should be discontinued. Use for short-term (8 to 12 weeks) only.[28456] INTENDED USE: Use as monotherapy only. Not recommended for patients who used any other anorectic agents within the prior year. Use is for patients with an initial body mass index (BMI) of 30 kg/m2 or more who have not responded to diet and exercise alone. The limited usefulness of agents of this class should be weighed against possible risks inherent in their use.[28456] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, short-term pharmacotherapy, such as with the amphetamine anorectics, has not been shown to produce longer-term health benefits in obese and overweight patients and cannot be generally recommended; these drugs should not be used for weight management long-term. Weight gain usually resumes after drug discontinuation.[62881]

    Children and Adolescents 12 years and older

    Initially, 25 to 50 mg PO once daily, preferably at mid-morning or mid-afternoon. Increase according to patient response, up to 50 mg PO 3 times daily. Max: 150 mg/day PO. Continue only if the patient has satisfactory weight loss within the first 4 weeks of treatment (i.e., weight loss of at least 4 pounds, or as determined by the physician). When tolerance to the anorectic effect develops, do not exceed the recommended dose in an attempt to increase the effect; instead, the drug should be discontinued. Use for short-term (8 to 12 weeks) only.[28456] INTENDED USE: Use as monotherapy only. Not recommended for patients who used any other anorectic agents within the prior year. Use is for patients with an initial body mass index (BMI) of 30 kg/m2 or more who have not responded to diet and exercise alone. The limited usefulness of agents of this class should be weighed against possible risks inherent in their use.[28456] Guidelines state that short-term pharmacotherapy, such as with the amphetamine anorectics, has not been shown to produce longer-term health benefits in pediatric patients and cannot be generally recommended. In general, children with a BMI below the 95th percentile should not be treated with antiobesity drugs. Pharmacotherapy for overweight children (BMI of at least 85th but less than 95th percentile) should be reserved for those with significant, severe comorbidities who have not responded to lifestyle modification.

    MAXIMUM DOSAGE

    Adults

    150 mg/day PO.

    Elderly

    150 mg/day PO.

    Adolescents

    150 mg/day PO.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Subsequent doses during the day, if given, should be administered at least 6 hours before bedtime to avoid interference with sleep.

    STORAGE

    Didrex:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Regimex:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

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

    Alcoholism, substance abuse

    Benzphetamine is contraindicated in patients with a history of substance abuse. Evaluate the child or adult patient for a personal and family history of abuse of prescription medicines or street drugs, or abuse or dependence on alcohol (alcoholism). Benzphetamine 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.

    Angina, arteriosclerosis, cardiac arrhythmias, cardiac disease, edema, hypertension, long QT syndrome, pulmonary hypertension, syncope, valvular heart disease

    Benzphetamine is contraindicated in patients with symptomatic cardiac disease (including cardiac arrhythmias), advanced arteriosclerosis, and moderate to severe hypertension. Due to its potential cardiac effects, benzphetamine should be avoided in patients with congenital long QT syndrome, known heart murmur, or valvular heart disease. Patients with even mild hypertension should be closely monitored while taking benzphetamine. Benzphetamine should not be used as part of combination therapy treatment of obesity (including treatment with prescription, over-the-counter, and herbal products); it should not be used in patients who used any anorectic agents within the prior year. In a case-control epidemiological study, there was an increased risk of developing pulmonary hypertension in patients taking anorectics; this risk was increased 23- fold in patients who used anorectic agents for longer than three months. While benzphetamine was not specifically studied in this case-control study, similar risks may apply. Conditions that may suggest the occurrence of pulmonary hypertension include the onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema; if these symptoms occur, discontinue benzphetamine immediately and evaluate for the possible presence of pulmonary hypertension. Combination therapy of benzphetamine with other anorectic agents (i.e., fenfluramine and dexfenfluramine) may have contributed to valvular heart disease in some patients; other possible contributing factors include use for extended periods of time and use of higher than recommended doses. However, no cases of this valvulopathy have been reported when benzphetamine has been used alone. When assessing the risk of valvular heart diseases or pulmonary hypertension versus the potential benefit of weight loss, a baseline cardiac evaluation should be considered to detect pre-existing disease. Echocardiogram during and after treatment could be useful for detecting any valvular disorders which may occur.

    MAOI therapy

    Benzphetamine is contraindicated in patients who have received MAOI therapy within the past 14 days due to the possibility of precipitating a hypertensive crisis.

    Hyperthyroidism, thyroid disease

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

    Seizure disorder

    Patients who experience seizures or who have a seizure disorder, or patients taking certain anti-seizure medications should use benzphetamine with caution. Benzphetamine may decrease the seizure threshold and increase the risk of experiencing seizures, particularly during excess CNS stimulation (e.g., benzphetamine overdosage). The effects of amphetamines on the seizure threshold, in normal therapeutic dosages, are less clear. If seizures occur in a patient on benzphetamine, drug discontinuation may be necessary.

    Diabetes mellitus

    Insulin and oral antidiabetic agent requirements in patients with diabetes mellitus may be altered in association with the use of anorectic drugs, including benzphetamine, and the concomitant dietary restrictions.

    Glaucoma

    Benzphetamine is contraindicated in patients with glaucoma due to the potential for sympathetic stimulation to block aqueous outflow and raise intraocular pressure.

    Neonates, pregnancy

    Benzphetamine is contraindicated during pregnancy. Weight loss offers no potential benefit to a pregnant woman and weight loss coupled with caloric restriction may result in fetal harm; therefore, anorectic agents such as benzphetamine should not be used in pregnancy. Non-teratogenic effects are known to occur in neonates who are born to mothers dependent on amphetamines including increased incidences of premature births, low birth weights, and physical withdrawal symptoms such as dysphoria, agitation, and significant lassitude. Patients who become pregnant while taking benzphetamine should be apprised of the potential hazards to the fetus. Another amphetamine, dextroamphetamine, was teratogenic and embryotoxic when administered to mice at doses 41 times the maximum recommended human dose (MRHD); embryotoxic effects were not observed in other species at dextroamphetamine doses 7 to 12.5 times the MRHD.

    Breast-feeding

    Women taking amphetamines, including benzphetamine, should refrain from breast-feeding. Amphetamines are excreted in human milk. The American Academy of Pediatrics (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.

    Children, growth inhibition

    Safety and effectiveness in pediatric patients have not been established. Use of benzphetamine as an anorectic is not recommended in children under 12 years of age. Benzphetamine is not intended for use in attention-deficit hyperactivity disorder (ADHD). Benzphetamine is pharmacologically similar to the amphetamines and, therefore, the potential for growth inhibition, if used in children and adolescents, is a concern. If benzphetamine is used in a pediatric patient, monitor height and weight parameters relative to age at treatment initiation and periodically thereafter; guidelines for ADHD recommend monitoring height and weight of patients receiving stimulants yearly, at minimum. Patients who are not growing as expected may need to have their treatment interrupted.

    Driving or operating machinery

    The use of benzphetamine 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.

    Surgery

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

    Radiographic contrast administration

    Amphetamines, such as benzphetamine, lower the seizure threshold. Because of a potential increased risk of seizures, amphetamines should not be used during intrathecal radiographic contrast administration. Amphetamines should be discontinued 48 hours before the myelography and should not be resumed until at least 24 hours after the procedure.

    Abrupt discontinuation

    Abrupt discontinuation of benzphetamine after chronic use is not recommended. Discontinuation can result in extreme fatigue, a depressed state, or other withdrawal symptoms. Gradual withdrawal of therapy is recommended.

    Tics, Tourette's syndrome

    Amphetamines may precipitate motor or phonetic tics in those with Tourette's syndrome. If benzphetamine must be used in such patients, administer under close supervision and at the lowest effective dose.

    Geriatric

    Clinical studies of benzphetamine did not include sufficient numbers of geriatric subjects aged 65 years of age or older to determine whether they respond differently from younger adults in the treatment of obesity. Use in the geriatric patient only if clearly needed; use of benzphetamine is not ordinarily recommended, and patients must be carefully screened for conditions for which avoidance of amphetamines is recommended. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range. Side effects of amphetamines or other stimulants are usually mild in adults over 50 years of age 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.

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

    Benzphetamine is contraindicated in patients who are in an agitated state. Amphetamines should be used cautiously in those with bipolar disorder or mania due to the potential for manic episodes to occur in such patients, particularly during chronic intoxication of the drug. An assessment should be performed prior to initiation of therapy to determine the risk for bipolar disorder. Due to its toxic effects in overdose, benzphetamine 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 stimulant medications for attention-deficit hyperactivity disorder (ADHD). Although these behaviors may be related to the ADHD itself and benzphetamine is used in patients with obesity, psychological disturbances have been reported in patients who receive an anorectic agent together with a restricted diet. Therefore, patients should be advised to promptly report any changes in mood or behavior while receiving benzphetamine. 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. Amphetamines may exacerbate psychosis (e.g., schizophrenia), other thought disorders, or behavioral disturbances. Depression may occur following abrupt withdrawal of benzphetamine.

    Anorexia nervosa, bulimia nervosa, obesity treatment

    Obesity treatment with benzphetamine should be initiated only in patients with an initial body mass index (BMI) of 30 kg/m2 or higher who have not responded to an appropriate weight reducing regimen, including diet and/or exercise. 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.

    Peripheral vascular disease, Raynaud's phenomenon

    Amphetamines 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 of amphetamines 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 the 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.

    ADVERSE REACTIONS

    Severe

    cardiomyopathy / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    pulmonary hypertension / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known

    Moderate

    psychosis / Early / 0-1.0
    euphoria / Early / 0-1.0
    hypertension / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    hallucinations / Early / Incidence not known
    mania / Early / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    delirium / Early / Incidence not known
    hyperthermia / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    physiological dependence / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    psychological dependence / Delayed / Incidence not known
    tolerance / Delayed / Incidence not known

    Mild

    dyspepsia / Early / 1.0-10.0
    nausea / Early / 1.0-10.0
    dysgeusia / Early / 1.0-10.0
    xerostomia / Early / 1.0-10.0
    insomnia / Early / 1.0-10.0
    headache / Early / 1.0-10.0
    dizziness / Early / 1.0-10.0
    abdominal pain / Early / 0-1.0
    vomiting / Early / 0-1.0
    diarrhea / Early / 0-1.0
    emotional lability / Early / 0-1.0
    anxiety / Delayed / 0-1.0
    anorexia / Delayed / 10.0
    restlessness / Early / 10.0
    syncope / Early / Incidence not known
    tremor / Early / Incidence not known
    fatigue / Early / Incidence not known
    photosensitivity / Delayed / Incidence not known
    rash / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    libido increase / Delayed / Incidence not known
    libido decrease / Delayed / Incidence not known
    paranoia / Early / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Acebutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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 benzphetamine. 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 benzphetamine. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Acetaminophen; Caffeine: (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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 benzphetamine. 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) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Acetaminophen; Codeine: (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Acetaminophen; Diphenhydramine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Acetaminophen; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Acetaminophen; Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Acetaminophen; Propoxyphene: (Major) During overdosage of propoxyphene, the central stimulant effects of benzphetamine may be potentiated and the combination may produce fatal convulsions.
    Acetaminophen; Tramadol: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and tramadol. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. An additive risk of seizures is also possible. Inform patients taking this combination of the possible increased risk of serotonin syndrome and seizures and monitor for adverse effects particularly after a dose increase or the addition of interacting medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Acetazolamide: (Moderate) Urinary alkalinizers, such as acetazolamide, result in decreased renal excretion of amphetamines. Monitor for amphetamine-related side effects. Avoid concomitant use in amphetamine overdose situations. Urinary alkalinizers increase the proportion of non-ionized metabolites of the amphetamine molecule, resulting in decreased renal excretion of these compounds. Alkaline urine will significantly increase the half-life of benzphetamine.
    Aclidinium; 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.
    Acrivastine; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Albiglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Albuterol: (Moderate) 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: (Moderate) 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.
    Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aliskiren; Amlodipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    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: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration.
    Amantadine: (Moderate) Careful observation is required when amantadine is administered concurrently with central nervous system (CNS) stimulants. An increase in stimulant effects, such as nervousness, irritability, insomnia, tremor, seizures, or cardiac arrhythmias may occur.
    Ambrisentan: (Minor) Sympathomimetics such as benzphetamine can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy of ambrisentan.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with benzphetamine 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. Benzphetamine may increase the risk of seizures.
    Amiloride: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Amiloride; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Amlodipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Atorvastatin: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Benazepril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Celecoxib: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Olmesartan: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Telmisartan: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amlodipine; Valsartan: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Ammonium Chloride: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Amoxapine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of indirect-acting sympathomimetics, such as amphetamine, however, the data are not consistent.
    Angiotensin II receptor antagonists: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
    Angiotensin-converting enzyme inhibitors: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Antacids: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration.
    Arformoterol: (Moderate) Caution and close observation should be used when arformoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Armodafinil: (Moderate) The use of armodafinil with other psychostimulants, including amphetamines, (e.g., dextroamphetamine, lisdexamfetamine, amphetamine) has not been studied. In a single-dose study of dextroamphetamine combined with modafinil, a racemic compound containing armodafinil, no pharmacokinetic interactions occurred but a slight increase in stimulant-associated side effects was noted. Patients receiving combination therapy of armodafinil with other psychostimulants should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related side effects.
    Ascorbic Acid, Vitamin C: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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 benzphetamine. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine. (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Avoid excessive caffeine intake during use of benzphetamine. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Avoid excessive caffeine intake during use of benzphetamine. Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (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.
    Aspirin, ASA; Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Atenolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Atenolol; Chlorthalidone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Atomoxetine: (Moderate) 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, amphetamines 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 benzphetamine with caution. Amphetamines may decrease the seizure threshold and 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; Chlorthalidone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use benzphetamine with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Benazepril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Benazepril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Bendroflumethiazide; Nadolol: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (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: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Betaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
    Bisoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    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.
    Bretylium: (Moderate) Monitor blood pressure closely when sympathomimetics are administered with bretylium. The pressor effects of catecholamines are enhanced by bretylium.
    Brimonidine; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Bromocriptine: (Moderate) Concurrent use of bromocriptine and some sympathomimetics such as amphetamines should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed an isometheptene-containing medication for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed a phenylpropanolamine-expectorant combination and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
    Brompheniramine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Brompheniramine; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    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.
    Budesonide; 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.
    Bumetanide: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Buprenorphine: (Moderate) If concomitant use of buprenorphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Buprenorphine; Naloxone: (Moderate) If concomitant use of buprenorphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Bupropion: (Major) The risk of seizures from the use of bupropion may be increased with concomitant use of CNS stimulants and anorectics that may induce seizures, including benzphetamine. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Bupropion; Naltrexone: (Major) The risk of seizures from the use of bupropion may be increased with concomitant use of CNS stimulants and anorectics that may induce seizures, including benzphetamine. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
    Buspirone: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and buspirone. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Caffeine: (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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: (Moderate) Avoid excessive caffeine intake during use of benzphetamine. 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: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration. (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Calcium Carbonate; Risedronate: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Calcium Carbonate; Simethicone: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Calcium-channel blockers: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Canagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Canagliflozin; Metformin: (Moderate) 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; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Captopril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Captopril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Carbamazepine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Carbetapentane; Chlorpheniramine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbetapentane; Pyrilamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbidopa; Levodopa: (Major) Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions or discontinuation of benzphetamine is 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 or discontinuation of benzphetamine is recommended if the two agents are used concurrently.
    Carbinoxamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Carbinoxamine; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Carbinoxamine; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    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: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Carvedilol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Chlophedianol; Dexbrompheniramine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorcyclizine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorothiazide: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Chlorpheniramine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorpheniramine; Codeine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Chlorpheniramine; Dextromethorphan: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Chlorpheniramine; Hydrocodone: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Chlorpheniramine; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Chlorthalidone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Chlorthalidone; Clonidine: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of clonidine. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Cinacalcet: (Moderate) Warn patients that there are potentially serious drug interactions between cinacalcet and prescription amphetamine therapy or illicit amphetamine use. The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as cinacalcet. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Citalopram: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and citalopram. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    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. (Major) Urinary alkalinizers, such as potassium citrate diminish the urinary excretion of benzphetamine. These medications increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of benzphetamine will be prolonged in the presence of potassium citrate. This combination should be avoided.
    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. (Major) Urinary alkalinizers, such as potassium citrate diminish the urinary excretion of benzphetamine. These medications increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of benzphetamine will be prolonged in the presence of potassium citrate. This combination should be avoided.
    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.
    Clemastine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Clevidipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Clobazam: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Clonidine: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of clonidine. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed.
    Cocaine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
    Codeine: (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Codeine; Guaifenesin: (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Codeine; Phenylephrine; Promethazine: (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Codeine; Promethazine: (Moderate) If concomitant use of codeine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Colchicine; Probenecid: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Cyclizine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Cyproheptadine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Dacomitinib: (Moderate) Warn patients that the risk of amphetamine toxicity, including serotonin syndrome, may be increased during concurrent use with dacomitinib. Concurrent use of dacomitinib, a strong CYP2D6 inhibitor, may increase exposure to the amphetamine increasing the risk for serotonin syndrome. If serotonin syndrome occurs, both the amphetamine and dacomitinib should be discontinued and appropriate medical treatment should be implemented.
    Dapagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Delavirdine: (Moderate) Warn patients that there are potentially serious drug interactions between delavirdine and prescription amphetamine therapy or illicit amphetamine use. The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as delavirdine. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Dexchlorpheniramine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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; Diphenhydramine; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of quinidine, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    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.
    Diltiazem: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Dimenhydrinate: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Diphenhydramine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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. (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Diphenhydramine; Ibuprofen: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Diphenhydramine; Naproxen: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Diphenhydramine; Phenylephrine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Dorzolamide; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Doxazosin: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving doxazosin and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as doxazosin.
    Doxylamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Doxylamine; Pyridoxine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    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.
    Dyphylline: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
    Dyphylline; Guaifenesin: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
    Empagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Linagliptin; Metformin: (Moderate) 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: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Enalapril; Felodipine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Enflurane: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of benzphetamine. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use. Dosages of benzphetamine should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Eplerenone: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of eplerenone. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive 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; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    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.
    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: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and escitalopram. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Esketamine: (Major) Closely monitor blood pressure during concomitant use of esketamine and an amphetamine. Coadministration of psychostimulants, such as amphetamines, with esketamine may increase blood pressure, including the possibility of hypertensive crisis.
    Eslicarbazepine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Esmolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Ethacrynic Acid: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Ethosuximide: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use benzphetamine with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of ethosuximide; the extent of absorption of these seizure medications is not known to be affected.
    Etomidate: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of sympathomimetics. Dosages of sympathomimetics 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: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Felodipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Fenfluramine: (Moderate) Use fenfluramine and amphetamines with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fentanyl: (Moderate) If concomitant use of fentanyl and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Fluoxetine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and fluoxetine. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. In addition, amphetamines are partially metabolized by CYP2D6 and fluoxetine is a strong CYP2D6 inhibitor. Increased systemic exposure to amphetamines from CYP2D6 inhibition may result in high blood pressure, tachycardia, anxiety, irritability, insomnia, or other amphetamine-related adverse effects.
    Fluoxetine; Olanzapine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and fluoxetine. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. In addition, amphetamines are partially metabolized by CYP2D6 and fluoxetine is a strong CYP2D6 inhibitor. Increased systemic exposure to amphetamines from CYP2D6 inhibition may result in high blood pressure, tachycardia, anxiety, irritability, insomnia, or other amphetamine-related adverse effects.
    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: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and fluvoxamine. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    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) Foods that acidify the urine may increase benzphetamine renal excretion. Conversely, foods that alkalinize the urine may slightly slow urinary excretion of amphetamines. Patients should not significantly alter their diets, however, as these changes are not expected to be clinically significant. (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.
    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: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Furosemide: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Gabapentin: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, 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, but not all, green tea products contain caffeine. Additive CNS stimulant effects are likely to occur when caffeine is coadministered with other CNS stimulants or psychostimulants. Caffeine should be avoided or used cautiously with benzphetamine.
    Guaifenesin; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Guanabenz: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of guanabenz when administered concomitantly. Patients should be monitored for loss of blood pressure control.
    Guanfacine: (Moderate) Sympathomimetic agents, such as amphetamines, may increase blood pressure and reduce the antihypertensive effects of antihypertensive agents, such as guanfacine. Monitor blood pressure and heart rate periodically when prescribed together. Guanfacine may be used adjunctively to psychostimulants such as amphetamines in the treatment of attention deficit hyperactivity disorder (ADHD). Pharmacokinetic studies reveal that guanfacine does not influence lisdexamfetamine pharmacokinetics and lisdexamfetamine does not affect guanfacine pharmacokinetics. No dosage adjustments are required when guanfacine and amphetamines are used together for ADHD. Monitor heart rate, blood pressure and for sedation during ADHD treatment.
    Homatropine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Hydrochlorothiazide, HCTZ; Losartan: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of methyldopa. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Hydrochlorothiazide, HCTZ; Moexipril: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Hydrochlorothiazide, HCTZ; Quinapril: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrochlorothiazide, HCTZ; Triamterene: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Hydrochlorothiazide, HCTZ; Valsartan: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Hydrocodone: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydrocodone; Ibuprofen: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydrocodone; Phenylephrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydromorphone: (Moderate) If concomitant use of hydromorphone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Hydroxyzine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    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.
    Ibuprofen; Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Iloprost: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Incretin Mimetics: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indapamide: (Moderate) Indapamide may increase blood levels and therefore potentiate the actions of amphetamines. Thiazide diuretics and related drugs like indapamide may increase urinary pH, acting as a urinary alkalinizer, thus reducing urinary excretion and increasing blood concentrations of the amphetamine. Co-administration of amphetamines and urinary alkalinizing agents should be avoided if possible. If needed, monitor for common amphetamine side effects, including decreased appetite, anxiety, dizziness, dry mouth, irritability, insomnia, nausea, increased blood pressure or increased heart rate.
    Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulins: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Iohexol: (Major) Sympathomimetics lower the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iopamidol: (Major) Sympathomimetics lower the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iopromide: (Major) Sympathomimetics lower the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Ioversol: (Major) Sympathomimetics lower the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Isocarboxazid: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Isosulfan Blue: (Major) Sympathomimetics lower the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Isradipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Ketamine: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of sympathomimetics. Dosages of sympathomimetics should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Labetalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Lacosamide: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Lamotrigine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Levalbuterol: (Moderate) 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: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Levobetaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Levobunolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Levodopa: (Major) Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions or discontinuation of benzphetamine is recommended if the two agents are used concurrently.
    Levorphanol: (Moderate) If concomitant use of levorphanol and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Levothyroxine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    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: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Lithium: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and lithium. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Loop diuretics: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Lopinavir; Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Lorcaserin: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and lorcaserin. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. Also, the safety and efficacy of coadministration of lorcaserin with other products for weight loss, including amphetamines, have not been established.
    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: (Moderate) Antacids and other gastrointestinal alkalinizing agents increase the oral absorption of amphetamines. This may lead to increased amphetamine concentrations. To help limit an interaction, do not take antacids at the same time as the amphetamine product. It is recommended to separate times of administration.
    Maprotiline: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
    Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Meclizine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Meperidine: (Moderate) If concomitant use of meperidine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Meperidine; Promethazine: (Moderate) If concomitant use of meperidine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Metaproterenol: (Major) Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Metformin: (Moderate) 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.
    Methadone: (Moderate) If concomitant use of methadone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Methazolamide: (Moderate) Urinary alkalinizers, such as methazolamide, result in decreased renal excretion of amphetamines. Monitor for amphetamine-related side effects. Avoid concomitant use in amphetamine overdose situations.
    Methenamine: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methenamine; Sodium Acid Phosphate: (Major) Urinary acidifying agents, such as ammonium chloride, phosphorus salts, and methenamine salts (e.g., methenamine; sodium acid phosphate), reduce the tubular reabsorption of amphetamines. As a result, amphetamine clearance is accelerated and the duration of effect is reduced. Combination therapy should be avoided if possible.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (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 sympathomimetics. Dosages of sympathomimetics should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Methyclothiazide: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Methyldopa: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of methyldopa. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive 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.
    Metolazone: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Metoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    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.
    Mirtazapine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and mirtazapine. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Modafinil: (Moderate) The use of modafinil with other psychostimulants, including amphetamines (e.g., amphetamine, dextroamphetamine. lisdexamfetamine), has not been extensively studied. Patients receiving combination therapy of modafinil with other psychostimulants should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other CNS stimulant-related side effects. In single-dose studies of dextroamphetamine combined with modafinil, no significant pharmacokinetic interactions occurred, but a slight increase in stimulant-associated side effects was noted.
    Moexipril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Molindone: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Monoamine oxidase inhibitors: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Morphine: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Morphine; Naltrexone: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
    Nadolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Nalbuphine: (Moderate) If concomitant use of nalbuphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Nebivolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Nebivolol; Valsartan: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Nefazodone: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and nefazodone. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Nicardipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    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: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Nimodipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Nisoldipine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Nitrates: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
    Non-Ionic Contrast Media: (Major) Sympathomimetics lower the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Omeprazole; Sodium Bicarbonate: (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.
    Oxycodone: (Moderate) If concomitant use of oxycodone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Oxymorphone: (Moderate) If concomitant use of oxymorphone and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Ozanimod: (Severe) Coadministration of ozanimod with amphetamines is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of amphetamines. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as amphetamines may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Amphetamines also have serotonergic effects that may increase blood pressure. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
    Paroxetine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and paroxetine. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. In addition, amphetamines are partially metabolized by CYP2D6 and paroxetine is a strong CYP2D6 inhibitor. Increased systemic exposure to amphetamines from CYP2D6 inhibition may result in high blood pressure, tachycardia, anxiety, irritability, insomnia, or other amphetamine-related adverse effects.
    Penbutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Perampanel: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Perindopril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Perindopril; Amlodipine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Phenelzine: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Phenobarbital: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use benzphetamine with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenobarbital; the extent of absorption of these seizure medications is not known to be affected.
    Phenoxybenzamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Phentermine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established.
    Phentermine; Topiramate: (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. (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established.
    Phentolamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Phenytoin: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use benzphetamine with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, the amphetamines may delay the intestinal absorption of phenytoin; the extent of absorption of these seizure medications is not known to be affected.
    Pindolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    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. (Major) Urinary alkalinizers, such as potassium citrate diminish the urinary excretion of benzphetamine. These medications increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of benzphetamine will be prolonged in the presence of potassium citrate. This combination should be avoided.
    Potassium Chloride: (Major) Urinary alkalinizers, such as potassium citrate diminish the urinary excretion of benzphetamine. These medications increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of benzphetamine will be prolonged in the presence of potassium citrate. This combination should be avoided.
    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. (Major) Urinary alkalinizers, such as potassium citrate diminish the urinary excretion of benzphetamine. These medications increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of benzphetamine will be prolonged in the presence of potassium citrate. This combination should be avoided.
    Potassium-sparing diuretics: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Pramlintide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Prazosin: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving prazosin and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as prazosin.
    Pregabalin: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Propofol: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of sympathomimetics. Dosages of sympathomimetics should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Propoxyphene: (Major) During overdosage of propoxyphene, the central stimulant effects of benzphetamine may be potentiated and the combination may produce fatal convulsions.
    Propranolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Quinapril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Quinidine: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of quinidine, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using racepinephrine inhalation are advised to avoid other non-prescription products containing sympathomimetics since additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate or blood pressure may be additive. Patients should avoid use of non-prescription decongestants, such as phenylephrine and pseudoephedrine, while using racepinephrine inhalations. Patients should avoid dietary supplements containing ingredients that are reported or claimed to have a stimulant or weight-loss effect, such as ephedrine and ephedra, Ma huang, and phenylpropanolamine. Patients taking prescription sympathomimetic or stimulant medications (including amphetamines, methylphenidate, dexmethylphenidate, isometheptane, epinephrine) should seek health care professional advice prior to the use of racepinephrine inhalations; consider therapeutic alternatives to racepinephrine for these patients.
    Ramipril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.
    Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Reserpine: (Major) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as reserpine, lowers the absorption of amphetamines, reducing their efficacy. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure such as reserpine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Ritonavir: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of ritonavir, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Rufinamide: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Safinamide: (Severe) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with amphetamines due to the risk of serotonin syndrome or hypertensive crisis. The manufacturer of safinamide recommends that a period of at least 14 days elapse between the discontinuation of safinamide and the initiation of serotonergic agents. Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications, such as amphetamines. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
    Salmeterol: (Moderate) 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. 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) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines 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: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin norepinephrine reuptake inhibitors. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Serotonin-Receptor Agonists: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Sertraline: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and sertraline. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    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 suppressants (e.g., benzphetamine). 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. Discontinue treatment with benzphetamine 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, methylphenidate, and modafinil are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
    Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and amphetamines, which are CNS stimulants. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
    Sotalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Spironolactone: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    St. John's Wort, Hypericum perforatum: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and St. John's Wort. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with amphetamines. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Sulfonylureas: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Tapentadol: (Moderate) If concomitant use of tapentadol and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Tedizolid: (Minor) Theoretically, drugs that possess MAO-inhibiting activity, such as tedizolid, can prolong and intensify the cardiac stimulation and vasopressor effects of amphetamines. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid, which is structurally similar to tedizolid, and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including amphetamines.
    Terazosin: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving terazosin and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as terazosin.
    Terbutaline: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. (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: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
    Thiazolidinediones: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Thiopental: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of sympathomimetics. Dosages of sympathomimetics 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: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
    Tipranavir: (Moderate) Warn patients that there are potentially serious drug interactions between tipranavir and prescription amphetamine therapy or illicit amphetamine use. The risk of amphetamine toxicity may be increased during concurrent use of potent CYP2D6 inhibitors such as tipranavir. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, discontinue both the amphetamine and CYP2D6 inhibitor and initiate appropriate medical treatment.
    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.
    Torsemide: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Tramadol: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and tramadol. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. An additive risk of seizures is also possible. Inform patients taking this combination of the possible increased risk of serotonin syndrome and seizures and monitor for adverse effects particularly after a dose increase or the addition of interacting medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Trandolapril: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
    Trandolapril; Verapamil: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised. (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Tranylcypromine: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Trazodone: (Moderate) Coadministration of trazodone and amphetamines may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. The MAOI activity of amphetamines may also be of concern with trazodone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. 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.
    Triamterene: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Tricyclic antidepressants: (Moderate) Use of amphetamines with tricyclic antidepressants may increase the risk for serotonin syndrome or have effects on blood pressure or heart rate. Monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. Also monitor blood pressure and heart rate. If the patient experiences changes in heart rate or rhythm, an ECG may be indicated. A dose reduction of one or both agents may be needed if side effects occur.
    Triprolidine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. 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.
    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.
    Tryptophan, 5-Hydroxytryptophan: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering amphetamines with other drugs that have serotonergic properties such as tryptophan. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Further study is needed to fully elucidate the severity and frequency of adverse effects that may occur from concomitant administration of amphetamines and tryptophan. Patients receiving tryptophan and an amphetamine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. The amphetamine and tryptophan should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Valproic Acid, Divalproex Sodium: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, discontinue the amphetamine.
    Vasodilators: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
    Verapamil: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Vigabatrin: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Vilazodone: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and vilazodone. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Vortioxetine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and vortioxetine. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    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: (Minor) Serotonin syndrome has been reported during the combined use of amphetamine stimulants and other medications with serotonergic properties. Serotonin syndrome has been reported during postmarketing use of ziprasidone; however, a causal relationship has not been established.
    Zonisamide: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.

    PREGNANCY AND LACTATION

    Pregnancy

    Women taking amphetamines, including benzphetamine, should refrain from breast-feeding. Amphetamines are excreted in human milk. The American Academy of Pediatrics (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.

    MECHANISM OF ACTION

    Benzphetamine is an anorectic agent that stimulates the central nervous system (CNS) and causes appetite suppression. The predominant mechanism of benzphetamine's CNS effect is to stimulate the release of several biogenic amines from storage sites in the nerve terminal. Benzphetamine is metabolized to amphetamine, and therefore has actions as both an indirect-acting sympathomimetic and a direct adrenergic agonist. At typical doses, benzphetamine stimulates the release of norepinephrine. At higher doses, dopamine is released from its storage sites accounting for some of the behavioral changes seen with sympathomimetics. The release of dopamine is thought to be responsible for the reinforcing properties of amphetamines. At still higher doses, the release of serotonin (5-hydroxytryptamine or 5-HT) is stimulated. Serotonin is this neurotransmitter that is thought to explain the overt psychotic behavior associated with amphetamine excess. The metabolite amphetamine may also act as a direct agonist on central 5-HT receptors. Indirect agonists are associated with tachyphylaxis due to the ever-decreasing supply of endogenous neurotransmitter that can be displaced from the nerve ending. Amphetamine may also inhibit monoamine oxidase (MAO), but this is a minor action. Amphetamine-induced CNS stimulation produces a decreased sense of fatigue, an increase in motor activity and mental alertness, and mild euphoria. These effects are believed to be due to stimulation of norepinephrine release from central noradrenergic neurons. The primary sites of activity in the CNS appear to be in the cerebral cortex and the reticular activating system. Benzphetamine's action in the treatment of obesity may result from mechanisms besides appetite suppression at the lateral hypothalamic feeding center. The anorectic effect is postulated to be secondary to CNS stimulation and a decrease in the acuity of smell and taste. Benzphetamine does 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.
     
    In the periphery, benzphetamine and its metabolite amphetamine are believed to stimulate the release of norepinephrine from the adrenergic nerve terminals, by direct action on alpha- and beta-receptors. Amphetamines increase systolic and diastolic blood pressure and cause respiratory stimulation and weak bronchodilation. Heart rate reflexively decreases in response to increased blood pressure. At higher doses and in overdose, heart rate may increase or cardiac arrhythmias may occur. Benzphetamine and amphetamine may produce mydriasis and contraction of the bladder sphincter. Benzphetamine's effect on GI tract motility is unpredictable.

    PHARMACOKINETICS

    Benzphetamine is administered orally. It is widely distributed throughout the body, including the CNS. Benzphetamine is metabolized in the liver to amphetamine and methamphetamine, as well as other metabolites. Urinary elimination may be affected by agents that acidify or alkalinize the urine (see Drug Interactions). For amphetamines in general, every 1 unit increase in urinary pH corresponds with a 7-hour increase in amphetamine half-life. Conversely, acidification of the urine speeds benzphetamine elimination.

    Oral Route

    The onset of action of benzphetamine occurs within 30—60 minutes after oral administration.