Dexmethylphenidate is a central nervous system (CNS) stimulant used to treat attention-deficit hyperactivity disorder (ADHD). It consists of the d-threo-enantiomer of methylphenidate, which is primarily responsible for the beneficial effects of racemic methylphenidate (the l-enantiomer appears to have negligible activity). Dexmethylphenidate is considered twice as potent as racemic methylphenidate. Researchers originally postulated that this increase in CNS potency might improve the adverse reaction profile when compared to racemic methylphenidate; however, actual clinical differences are uncertain. Stimulant medications, such as dexmethylphenidate, are considered first-line agents for ADHD. When compared to amphetamines, methylphenidate stimulants have equal efficacy and a similar adverse reaction profile. Peripheral pharmacologic activities are milder than those of the amphetamines, slightly decreasing the likelihood of appetite suppression and tic exacerbation. Stimulants have been associated with sudden death in patients with structural cardiac abnormalities or other serious cardiac disease when used at recommended ADHD doses; patients with structural heart defects, cardiomyopathy, coronary artery disease, serious cardiac arrhythmias, or other serious cardiac disease may be at risk for adverse cardiac events. The American Academy of Pediatrics and the American Heart Association recommend careful screening of all children and adolescents prior to initiating pharmacologic therapy for ADHD, including a detailed patient and family history and physical examination; any significant findings should be further assessed and referred for consultation with a pediatric cardiologist prior to initiating treatment.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations:
-A MedGuide is available which informs patients about the cardiac and psychiatric risks associated with use, and should be provided by the authorized dispenser to each patient receiving a prescription.
-Immediate-release tablets: Administer twice daily, with doses at least 4 hours apart. Depending on the patient's needs, twice-daily dosages may be administered in the morning and around noon. Individualized timing of the midday dose may be necessary. May be administered with or without food.
-Once-daily extended-release capsules: Administer once daily in the morning. May be administered without regard to meals and swallowed whole with the aid of liquids. Do NOT crush, chew, or cut in half. If swallowing is difficult, the capsule may be opened and the contents gently sprinkled on one tablespoon of cold applesauce (not warm- warm applesauce could change the characteristics of the medication) and swallowed. The capsule contents (beads) should not be crushed or chewed. Prepare the sprinkle dose just prior to administration (do not store for future use). Drinking some fluids (e.g., water, milk or juice), should follow the intake of the sprinkles with applesauce.
The adverse side effects of dexmethylphenidate are relatively frequent but usually mild at normally prescribed dosages. The side effects may be more frequent or severe with the initial days of therapy. Most side effects disappear within a few weeks of continued use. Overall, 50 of 684 children (7.3%) treated with immediate-release dexmethylphenidate during clinical studies experienced an ADR that resulted in discontinuation and none of the 53 pediatric patients receiving extended-release dexmethylphenidate discontinued treatment due to an adverse event. During clinical trial evaluation of extended-release dexmethylphenidate in adults, 10.7% of patients receiving active treatment discontinued treatment compared to 7.5% of placebo-treated patients.
During clinical trials of immediate-release or extended-release dexmethylphenidate for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents, gastrointestinal (GI) adverse effects that occurred in at least 5% of patients receiving dexmethylphenidate and with an incidence of at least twice that of patients in the placebo group included: dyspepsia (8% vs. 4%), decreased appetite (30% vs. 9%), anorexia (6% vs. 1%), nausea (9% vs. 1%), and abdominal pain (15% vs. 6%). In a separate placebo-controlled fixed-dose study in pediatrics, the following dose-related GI effects were reported versus placebo: vomiting (2% to 9% vs. 24%) and anorexia (5% to 7% vs. 0%). In an adult study, dose-related effects occurring more frequently with dexmethylphenidate than placebo included xerostomia (7% to 20% vs. 4%) and dyspepsia (5% to 9% vs. 2%). Approximately 1.2% of adult patients and 1% of pediatric patients discontinued treatment due to anorexia. Diarrhea and constipation have also been reported with other methylphenidate-containing products. In pediatric patients, loss of appetite, abdominal pain, and weight loss during prolonged treatment may occur more frequently than other effects associated with the drug. Anorexia and other appetite changes occur in many pediatric patients in the first days of therapy. Eating small, frequent meals or snacks may help limit appetite problems. Xerostomia may be limited by sucking sugarless hard candy, crushed ice, and drinking plenty of water or other fluids. Abdominal pain is generally mild and infrequent and may respond to dosage reduction if it becomes a continual problem for the patient. Monitor height and weight parameters relative to age at the initiation of treatment and periodically during therapy; interrupt treatment in patients who are not growing or gaining weight as expected.
During a clinical trial of extended-release dexmethylphenidate for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents, centrally-mediated adverse effects that occurred in at least 5% of patients receiving dexmethylphenidate and with an incidence of at least twice that of patients in the placebo group included: headache (25% vs. 11%) and insomnia (5% to 17% vs. 3%). In an adult study, headache (26% to 39% vs. 19%) occurred more frequently with dexmethylphenidate than placebo and was dose-related. Other events occurring more frequently with dexmethylphenidate than placebo included feeling jittery or restlessness (12% vs. 2%) and dizziness (6% vs. 2%). In adult clinical trials, 1.8% of patients discontinued treatment due to insomnia or feeling jittery, and in pediatric trials, approximately 1% discontinued treatment due to insomnia. Mild euphoria may occur in the first weeks of treatment. Convulsions (seizures) and drowsiness have also been reported with dexmethylphenidate use. Fatigue and migraine have been reported with other methylphenidate-containing products. Nervousness and insomnia are common adverse effects during the use of methylphenidate products and may occur more frequently in pediatric patients. These effects may be limited by dosage reduction or omitting the afternoon or evening doses. Insomnia and restlessness will typically resolve within a few days of use, provided the dosage is appropriate, and doses are not administered within 6 hours of bedtime. Avoidance of exercising late in the day, limiting caffeinated beverages, and setting regular bedtime schedules may limit sleep disruption. Interrupted sleep patterns may indicate a need for dosage reduction. Once-daily morning dosing may be effective in some patients and may also help to limit intolerable side effects.
During a clinical trial of extended-release dexmethylphenidate for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents, anxiety occurred in at least 5% of patients receiving dexmethylphenidate and with an incidence of at least twice that of patients in the placebo group (6% vs. 0%). In a separate placebo-controlled fixed-dose study in pediatric patients, the following psychiatric effects occurred more frequently with active treatment than placebo: depression (0% to 3% vs. 0%), emotional lability (0% to 3% vs. 2%), and irritability (0% to 5% vs. 0%). In an adult study, anxiety (5% to 11% vs. 2%) occurred more frequently with dexmethylphenidate than placebo and was dose-related. In adult clinical trials, 1.2% of patients discontinued treatment due to anxiety. Disorientation and libido changes (libido decrease or libido increase) have been reported with other methylphenidate-containing products. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and postmarketing experience with medications used to treat ADHD. Although causality to the drugs has not been established and these behaviors are often observed in children and adolescents with ADHD, close monitoring is recommended. Patients and their caregivers should be advised to promptly report any changes in mood or behavior. If suicide-related events emerge during treatment, consideration should be given to dose reduction or drug discontinuation, especially if symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Treatment emergent psychotic or manic symptoms (e.g., psychosis, hallucinations, delusional thinking, or mania) in patients without a prior history of such events can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% of stimulant-treated patients compared to 0% placebo. In a cohort study assessing 221,846 adolescents and young adults who received a prescription for a stimulant for ADHD, new-onset psychosis occurred in approximately 1 in 660 patients. The percentage of patients who had a psychotic episode was 0.1% in patients receiving methylphenidate compared to 0.21% in patients receiving amphetamine (hazard ratio with amphetamine use, 1.65; 95% CI 1.31 to 2.09). The median time from when the stimulant was dispensed to the psychotic episode was 128 days. Clinicians should be aware that while such effects are relatively common with both ADHD and stimulant use, excessive symptoms (agitation, euphoria, delirium, confusion, hallucinations) may be a sign of excessive dosage or toxicity.
During clinical trials of dexmethylphenidate in pediatric patients for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), 1 of the most common reasons for treatment discontinuation was twitching (described as motor or vocal tics, 1% incidence). Arthralgia, dyskinesia, muscle cramps, rhabdomyolysis, and tremor have also been reported with dexmethylphenidate; stimulant-induced rhabdomyolysis is most often associated with sympathomimetic toxicity. Myalgia has been reported with other methylphenidate-containing products.
Growth inhibition is a possible long-term side effect of the use of stimulants in children; proposed mechanisms have included the suppression of appetite or an alteration in growth hormone secretion. Some have suggested that the use of drug holidays will allow growth to 'catch-up'. However, drug holidays are typically reserved for children with well-controlled ADHD symptoms, and drug holidays are of unproved value in limiting growth suppression. Growth rebound has been observed after the discontinuation of the stimulants in children and clinical studies do not indicate that methylphenidate compromises the attainment of normal adult height and weight. Practitioners should monitor for this side effect during dexmethylphenidate therapy by monitoring height and weight parameters relative to age at the initiation of treatment and periodically during therapy (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. In a 24-month follow-up, the MultiModal Treatment Study showed a deceleration of growth of roughly 1 cm per year with stimulant use. In general, growth remained in the normal curve for most children, except those in the lowest percentiles of height for age. Data obtained on the effects of stimulants on growth suppression in children 7-10 years of age suggested that regularly medicated children (7 days/week) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years.
Cardiovascular events, including sudden death, have been associated with stimulant use in both adult and pediatric patients. Cardiovascular or cerebrovascular effects associated with dexmethylphenidate or methylphenidate use range in severity from mild to life-threatening and include cardiac murmur, palpitations, angina, chest pain (unspecified), cardiac arrhythmia (arrhythmia exacerbation), sinus tachycardia, bradycardia, hypertension, hypotension, myocardial infarction, stroke, and cerebral arteritis or occlusion. In a nationwide self-controlled case series (n = 1,224), use of methylphenidate in children and adolescents was associated with an increased risk of arrhythmia during the first 8 weeks of therapy (incidence rate ratio [IRR] 1.61; 95% CI 1.48 to 1.74), with the highest risk observed within the first 3 days of treatment (IRR 2.01; 95% CI 1.74 to 2.31) and in those with congenital heart disease (IRR 3.49; 95% CI 2.33 to 5.22). Overall, no significant risk of myocardial infarction was observed, but risk was elevated after the first week of treatment through week 8. Sinus tachycardia may be more common in children than adults. During pediatric clinical trials of dexmethylphenidate, tachycardia was responsible for drug discontinuation in approximately 1% of study participants. In general, stimulant medications at usual doses increase heart rate and blood pressure by an average of 3 to 6 bpm and 2 to 4 mmHg, respectively. The effect of single doses of 40 mg extended-release dexmethylphenidate on the corrected QT interval (QTcF) was evaluated in healthy adult volunteers; dexmethylphenidate did not prolong the QTc interval to any clinically relevant extent. Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during dexmethylphenidate treatment should undergo a prompt cardiac evaluation. Minor manifestations of any of these symptoms may indicate a need for dosage reduction or discontinuation. Severe cardiac adverse effects (e.g., arrhythmia, tachycardia) may be associated with dexmethylphenidate toxicity; evaluate patients carefully who present with cardiac symptoms for possible overdose. Dexmethylphenidate should be used with caution in patients with conditions that would be expected to worsen by an increase in heart rate or blood pressure. Pulse and blood pressure measurements should be obtained at baseline, after dosage increases, and periodically throughout dexmethylphenidate therapy.
The onset or exacerbation of motor and verbal tics has been reported with use of methylphenidate-class products. In clinical trials of pediatric patients treated with dexmethylphenidate, 1% of patients discontinued treatment due to motor or verbal tics. Patients should be monitored for the emergence or worsening of tics or Tourette's syndrome; consider a dose reduction or discontinuation of treatment if clinically indicated.
Hypersensitivity reactions, including anaphylactoid reactions and angioedema, have been reported with dexmethylphenidate. In addition, immune reactions including rash, urticaria, fever, exfoliative dermatitis, erythema multiforme, thrombocytopenic purpura, vasculitis, and alopecia have also been reported. Pruritus was reported in 3% or less of pediatric patients during dexmethylphenidate clinical trials and was considered dose-related.
Liver abnormalities, including elevated hepatic enzymes and severe hepatic injury (hepatic failure), have been reported with dexmethylphenidate. Hyperbilirubinemia has also been reported with other methylphenidate-containing products.
Psychological dependence, physiological dependence, and tolerance may occur with dexmethylphenidate therapy. Abrupt discontinuation or a significant dose reduction of CNS stimulants after prolonged use may produce withdrawal symptoms that include dysphoria, depression, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor retardation or agitation.
Stimulants used to treat ADHD, including dexmethylphenidate, are associated with peripheral vasculopathy. Effects of peripheral vasoconstriction, including Raynaud's phenomenon, were observed in postmarketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor for digital changes during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
The sympathetic stimulation of stimulants, including dexmethylphenidate, may block aqueous outflow and raise intraocular pressure, exacerbating ocular hypertension or glaucoma. Visual impairment such as blurred vision, mydriasis, diplopia, ocular pain, and accomodation disorder have been reported with stimulant use. Patients should report any new or worsening visual disturbance; ophthalmic examination may be required.
Dexmethylphenidate overdosage primarily presents as central nervous system overstimulation and excessive sympathomimetic effects. Signs and symptoms of toxicity may include vomiting, agitation, tremor, hyperreflexia, muscle twitching, euphoria, confusion, hallucinations, delirium, hyperhidrosis, flushing, headache, hyperthermia, tachycardia, hypertension, palpitations, hypotension, mydriasis, and dryness of mucous membranes. Severe manifestations of dexmethylphenidate overdose include cardiac arrhythmias, seizures, rhabdomyolysis, and coma. Treatment consists of appropriate supportive measures.
Frequent or prolonged erections and priapism, sometimes requiring surgical intervention, have been reported with methylphenidate products, such as dexmethylpheindate, in both adult and pediatric patients. Prolonged erections (more than 4 hours) in male patients should be promptly reported, as immediate diagnosis and treatment are essential to avoid tissue damage. Priapism can occur in males of any age; younger males, particularly those who have not reached puberty, may not recognize the problem or may be embarrassed to tell anyone if it occurs. In a review of methylphenidate products by the FDA, the median age of patients who experienced priapism was 12.5 years (range: 8 to 33 years). Reported cases of priapism did not occur with drug initiation, but have occurred after a period of time on stimulant therapy and often subsequent to a dose increase. Priapism has also been reported during periods of drug withdrawal (e.g., drug holidays or discontinuation). Caution should be used when considering changing male patients from stimulant to non-stimulant medications; atomoxetine is also associated with priapism in young males and appears to carry a higher risk of the condition compared to methylphenidate. Gynecomastia has also been reported with other methylphenidate-containing products.
Hematologic disorders, including anemia, leukopenia, and thrombocytopenia, have been reported with dexmethylphenidate. Pancytopenia and hematuria have also been reported with other methylphenidate-containing products. Periodic monitoring of blood counts is advisable for those on chronic therapy.
During a fixed-dose study of extended-release dexmethylphenidate for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents, nasal congestion (0% to 5%) occurred more frequently with dexmethylphenidate than placebo and was dose-related. The following side effects occurred in treated adults at rates higher than with placebo: pharyngolaryngeal pain (4% to 7%), Fever, cough, dyspnea, and naso-pharyngitis have also been reported with dexmethylphenidate and/or with other methylphenidate-class products.
Dexmethylphenidate is contraindicated in patients with known hypersensitivity to dexmethylphenidate, methylphenidate, or any components of these products.
CNS stimulants should be used with caution in those with bipolar disorder or a pre-existing psychotic disorder (e.g., schizophrenia). CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychosis. These medications can also induce mania or a mixed episode in patients with bipolar disorder. Prior to initiating treatment with dexmethylphenidate, screen patients for risk factors for bipolar disorder or developing an episode of mania (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression). At recommended doses, CNS stimulants may also cause psychotic or manic symptoms (such as hallucinations, delusions, or mania) in patients without a prior history of psychosis or mania. Advise patients and their caregivers to promptly report suicidal ideation or any changes in mood or behavior and consider discontinuing treatment if these symptoms occur.
Central nervous system (CNS) stimulants, such as dexmethylphenidate, have a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Caution is recommended in patients with a known history of substance abuse, including alcoholism; evaluate patients for a personal or family history of abuse or dependence on alcohol (alcoholism), prescription medications, or street drugs. Assess each individual's risk for abuse, misuse, or addiction before prescribing a CNS stimulant, and monitor for the development of these behaviors or conditions throughout treatment. Children and adolescents with attention-deficit hyperactivity disorder (ADHD) are more prone to substance abuse compared to those without ADHD, and those with co-occurring mental health conditions (e.g., depression, disruptive behavior disorders) are at even greater risk; however, appropriate treatment of ADHD with medication and behavior therapy may reduce the risk of developing a substance abuse disorder. The American Academy of Pediatrics recommends an active substance abuse disorder be treated appropriately before beginning stimulant medication. In patients with well-documented ADHD that predates the onset of substance abuse, a careful risk/benefit assessment must be conducted and appropriate consultation (e.g., a psychiatrist or addiction specialist) is suggested. To reduce the risk of substance abuse in patients who are prescribed stimulants, prescribers should take special care to 1.) confirm an accurate diagnosis of ADHD, 2.) screen older children and adolescents for use of alcohol, marijuana, and other drugs, 3.) provide age-appropriate anticipatory guidance (e.g., discuss proper medication use, risk of misuse, diversion, and abuse, safe storage of medication, appropriate transition to self-administration in older children), and 4.) carefully document and monitor prescription records closely. Prescribing and dispensing the smallest appropriate quantity may help to minimize abuse, misuse, and overdosage. CNS stimulants can be diverted for non-medical use into illicit channels or distribution. The most common source of non-medical use is sharing from family or friends with misuse of the patient's own prescription or obtaining from illicit channels occurring less frequently. Sharing of CNS stimulant medications can lead to substance abuse disorder and addiction in those they are shared with. Misuse and abuse of CNS stimulants can result in potential for overdose or poisoning and death; the risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Educate patients and their families about these risks, proper storage, and proper disposal of any unused medication. Misuse or abuse may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with stimulant abuse or misuse.
CNS stimulant medications, including dexmethylphenidate, can cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 beats per minute). Some individuals may have larger increases. Monitor all patients receiving dexmethylphenidate for hypertension and tachycardia.
Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosages. Avoid use of CNS stimulants in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease. Prior to initiating any CNS stimulant, carefully assess patient for the presence of cardiac disease (i.e., perform a careful patient history, assess for any family history of sudden death or ventricular arrhythmia, and complete a physical exam) and counsel patients to report symptoms of cardiac disease (i.e., exertional chest pain, unexplained syncope) immediately. Although it is reasonable for a health care provider to obtain an ECG as part of the cardiovascular evaluation, it is not mandatory. Treatment with stimulants should not be withheld because an ECG is not performed. However, any patient with significant findings on physical examination, ECG, or from patient or family history (such as known congenital heart disease, structural heart disease, arrhythmias, or a family history of sudden cardiac death in members younger than 35 years of age) should be referred for consultation with a pediatric cardiologist prior to starting the stimulant medication. Overall, studies have not shown an association between the use of ADHD medications and adverse cardiovascular events; however, long-term cardiovascular risks associated with ADHD medications are unknown. Careful monitoring should be performed after initiation of stimulant medications; if any abnormal findings or arrhythmias are diagnosed during treatment, consider discontinuation of the stimulant.
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Monitor for growth inhibition by monitoring height and weight parameters relative to age at treatment initiation and periodically thereafter (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted.
The safety of dexmethylphenidate during human pregnancy has not been established. Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects; however, there may be risks to the fetus associated with the use of CNS stimulants during pregnancy. CNS stimulants can cause vasoconstriction and thereby decrease placental perfusion. Several cohort studies have reported an increased risk of spontaneous abortion, pre-eclampsia, preterm birth, and perinatal complications associated with the use of methylphenidate during pregnancy while other studies have also shown an increase in these complications in unmedicated women with ADHD. Treatment with methylphenidate has also been associated with a small increased risk of cardiac malformations in some studies, while other studies have shown no increase in risk when controlling for concomitant medications and medical comorbidities in the mother. Premature delivery and low birth weight infants have also been reported in mothers taking stimulants while pregnant. Neonates with in utero exposure to stimulants may experience withdrawal after delivery; monitor the newborn for symptoms of withdrawal such as feeding difficulty, irritability, agitation, and excessive drowsiness. When deciding whether to continue, adjust, or stop the medication in a pregnant patient, it is important to weigh the risk of the medication against the risk of untreated illness and how these issues may affect both the mother and the unborn child. The National Pregnancy Registry for ADHD medications is dedicated to evaluating the safety of ADHD medication exposure during pregnancy. Healthcare providers are encouraged to register patients at https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/ or by calling 1-866-961-2388.
When considering the use of dexmethylphenidate during breast-feeding, assess the developmental and health benefits of breast-feeding, along with the potential risks of infant drug exposure, and the risk of an untreated or inadequately treated maternal condition. Dexmethylphenidate has a low molecular weight and should be expected to be excreted in human breast milk. Based on limited information from case reports on the use of racemic methylphenidate during breast-feeding, the calculated infant daily dose for an exclusively breast-fed infant would be about 0.2% to 0.7% of the maternal weight adjusted dose and a milk-to-plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant and no effects on milk production. Although dexmethylphenidate may be considered as an alternative to other stimulants during lactation and breast-feeding, the medical use of stimulant medications during breast-feeding has not been formally evaluated. If breast-feeding cannot be avoided during the use of dexmethylphenidate, the nursing infant should be monitored for signs of central nervous system hyperactivity, such as decreased appetite, reduced weight gain, insomnia, and agitation. The effect of stimulant medication exposure via breast milk on the long-term neurological development of the infant is not known.
Concomitant use of halogenated anesthetics and dexmethylphenidate may increase the risk of sudden blood pressure and heart rate increase during surgery. Monitor blood pressure and avoid use of dexmethylphenidate in patients being treated with anesthetics on the day of surgery.
Dexmethylphenidate is not FDA-approved for obesity treatment. Eating disorders, such as anorexia nervosa or bulimia nervosa, should be ruled out prior to treatment with stimulants. Patients with eating disorders may have physiologic complications and metabolic abnormalities that increase their risk of drug-induced adverse effects. Because stimulants are known to cause appetite suppression and weight loss, the potential for abuse in patients with eating disorders should be considered.
Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of dexmethylphenidate; use with caution in elderly patients, given the greater incidence of cardiac disease or other conditions in these patients. Extended-release dexmethylphenidate (Focalin XR) has not been systematically studied in the geriatric population. Stimulant medications are used as the treatments of choice in the adult patient over 50 years of age with ADHD when behavioral and lifestyle modifications alone have failed to improve concerns associated with inattention, such as task focus and completion, or organization and time management. Medication should be titrated with low doses initially and with a slow increase. Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of the amphetamines; use with caution in the older adult. Side effects of amphetamines or other stimulants are usually mild but may include mood or behavior changes, tremor, insomnia, increased blood pressure, headache, or gastroesophageal reflux or other GI complaints. Adults should have their blood pressure and heart rate checked at baseline and periodically during treatment. If treatment is considered necessary, periodically re-evaluate the long-term usefulness of the drug for the individual patient.
Dexmethylphenidate is contraindicated in patients who have received MAOI therapy within the past 14 days because of the possibility of precipitating a hypertensive crisis.
Stimulant medications are associated with peripheral vasculopathy, including Raynaud's phenomenon. Worsening of peripheral vascular disease is possible. Effects on circulation have been observed with therapeutic doses at different times throughout therapy in all age groups. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor all patients for digital changes during treatment with stimulant medications, especially those with pre-existing circulation problems. Instruct patients to seek immediate medical attention if any new digital numbness, pain, skin discoloration, or temperature sensitivity occur, or if unexplained wounds appear on their fingers or toes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
Psychological dependence, physiological dependence, and tolerance may occur with dexmethylphenidate therapy. Abrupt discontinuation or a significant dose reduction of CNS stimulants after prolonged use may produce withdrawal symptoms that include dysphoria, depression, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor retardation or agitation. Consider monitoring for withdrawal symptoms after significant dose reduction or discontinuation after prolonged use.
CNS stimulants, including dexmethylphenidate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette's syndrome has also been reported. Prior to initiating dexmethylphenidate, carefully assess family history and clinically evaluate patients for motor or verbal tics or Tourette's syndrome. Regularly monitor dexmethylphenidate-treated patients for the emergence or worsening of tics or Tourette's syndrome and discontinue treatment if clinically appropriate.
Dexmethylphenidate should be used cautiously in patients at risk of glaucoma. Increased intraocular pressure (IOP) and angle closure glaucoma have been reported in association with dexmethylphenidate treatment. While the mechanism is not clear, dexmethylphenidate-treated patients considered at risk for acute angle closure glaucoma (e.g. patients with significant hyperopia) should be evaluated by an ophthalmologist. Patients with a history of open-angle glaucoma or abnormally increased IOP should only receive dexmethylphenidate if the benefit of treatment outweighs the risk. These patients should be monitored closely for changes in vision. Visual disturbance has been reported with the use of dexmethylphenidate and may present as difficulties with accommodation and blurring of vision.
For the treatment of attention-deficit hyperactivity disorder (ADHD):
-for the treatment of ADHD in persons naive to methylphenidate or switching from a stimulant other than methylphenidate:
Oral dosage (immediate-release):
Adults*: 2.5 mg PO twice daily, initially. May increase the dose by 2.5 to 5 mg/day at weekly intervals based on clinical response. Max: 50 mg/day. Reduce dose or, if necessary, discontinue therapy if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue therapy.
Children and Adolescents 6 to 17 years: 2.5 mg PO twice daily, initially. May increase the dose by 2.5 to 5 mg/day at weekly intervals based on clinical response. The FDA-approved maximum dose is 20 mg/day. However, a maximum dose of 50 mg/day may be considered. Reduce dose or, if necessary, discontinue therapy if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue therapy.
Oral dosage (extended-release):
Adults: 10 mg PO once daily in the morning, initially. May increase the dose by 10 mg/day at weekly intervals based on clinical response. The FDA-approved maximum dose is 40 mg/day. However, a maximum dose of 50 mg/day may be considered. Reduce dose or, if necessary, discontinue therapy if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue therapy.
Children and Adolescents 6 to 17 years: 5 mg PO once daily in the morning, initially. May increase the dose by 5 mg/day at weekly intervals based on clinical response. The FDA-approved maximum dose is 30 mg/day. However, a maximum dose of 50 mg/day may be considered. Reduce dose or, if necessary, discontinue therapy if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue therapy.
-for the treatment of ADHD in persons currently receiving methylphenidate:
Oral dosage (immediate-release):
Children and Adolescents 6 to 17 years: 50% of total daily dose of racemic methylphenidate given as dexmethylphenidate PO in 2 divided doses, initially. May increase the dose by 2.5 to 5 mg/day at weekly intervals based on clinical response. The FDA-approved maximum dose is 20 mg/day. However, a maximum dose of 50 mg/day may be considered. Reduce dose or, if necessary, discontinue therapy if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue therapy.
Oral dosage (extended-release):
Adults: 50% of total daily dose of racemic methylphenidate given as dexmethylphenidate PO once daily in the morning, initially. Persons taking immediate-release dexmethylphenidate may be switched to extended-release dexmethylphenidate at the same total daily dose taken once daily. May increase the dose by 10 mg/day at weekly intervals based on clinical response. The FDA-approved maximum dose is 40 mg/day. However, a maximum dose of 50 mg/day may be considered. Reduce dose or, if necessary, discontinue therapy if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue therapy.
Children and Adolescents 6 to 17 years: 50% of total daily dose of racemic methylphenidate given as dexmethylphenidate PO once daily in the morning, initially. Persons taking immediate-release dexmethylphenidate may be switched to extended-release dexmethylphenidate at the same total daily dose taken once daily. May increase the dose by 5 mg/day at weekly intervals based on clinical response. The FDA-approved maximum dose is 30 mg/day. However, a maximum dose of 50 mg/day may be considered. Reduce dose or, if necessary, discontinue therapy if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue therapy.
Maximum Dosage Limits:
-Adults
20 mg/day PO immediate-release formulation; 40 mg/day PO extended-release formulation.
-Geriatric
20 mg/day PO immediate-release formulation; 40 mg/day PO extended-release formulation.
-Adolescents
20 mg/day PO immediate-release formulation and 30 mg/day PO extended-release formulation (FDA-approved labeling); however, up to 50 mg/day PO has been used off-label (both formulations).
-Children
6 to 12 years: 20 mg/day PO immediate-release formulation and 30 mg/day PO extended-release formulation (FDA-approved labeling); however, up to 50 mg/day PO has been used off-label (both formulations).
1 to 5 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; use with caution, as dexmethylphenidate is metabolized by the liver.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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 dihydrocodeine and methylphenidate derivatives 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; Pyrilamine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Codeine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives 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; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Acetaminophen; Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives 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 methylphenidate derivatives 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; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with methylphenidate derivatives. 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: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including aliskiren. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidates and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including aliskiren. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidates and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Alogliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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-blockers: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
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.
Amantadine: (Moderate) Use of amantadine with methylphenidate derivatives, which are CNS stimulants, requires careful observation. Coadministration may increase the risk of stimulant effects, such as nervousness, irritability, insomnia, tremor, seizures, or cardiac arrhythmias.
Ambrisentan: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidates and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with methylphenidate derivatives 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. Methylphenidate derivatives may increase the risk of seizures.
Amiloride: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Amitriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Amlodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Atorvastatin: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Benazepril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Celecoxib: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Olmesartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Amoxapine: (Moderate) Methylphenidate derivatives and amoxapine may lower the seizure threshold; therefore, caution is particularly advisable when this combination is administered to patients susceptible to seizures. In addition, methylphenidate is thought to exert some of its beneficial effects through dopamine re-uptake blockade while amoxapine has central dopamine antagonist properties. In theory, the therapeutic effects of either agent may be reduced.
Angiotensin II receptor antagonists: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Angiotensin II: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Angiotensin-converting enzyme inhibitors: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Apomorphine: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Armodafinil: (Major) The use of armodafinil with other psychostimulants, including methylphenidate derivatives, has not been studied. Patients receiving combination therapy of armodafinil with other psychostimulants should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related side effects.
Articaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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 methylphenidate or its derivatives 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; Oxycodone: (Moderate) If concomitant use of oxycodone and methylphenidate derivatives 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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Azilsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Benazepril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Beta-blockers: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Betaxolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
Bexagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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.
Bisoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bretylium: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Brimonidine; Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bromocriptine: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as bromocriptine. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Brompheniramine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Bumetanide: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Bupivacaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Buprenorphine: (Moderate) If concomitant use of buprenorphine and methylphenidate derivatives 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 methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Bupropion: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Bupropion; Naltrexone: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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 methylphenidate or its derivatives 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.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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 methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate derivatives. 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) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Caffeine; Sodium Benzoate: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. 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, Magnesium, Potassium, Sodium Oxybates: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. 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. Note that CNS stimulants, including methylphenidate, are frequently used in the treatment of narcolepsy, and clinical trials involving the use of psychostimulants with sodium oxybate have not found the combinations to be unsafe. Pharmacodynamic interactions cannot be ruled out, however.
Calcium-channel blockers: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Canagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Captopril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Carbamazepine: (Minor) Psychostimulants, such as methylphenidate and its derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as carbamazepine. There are rare case reports of reduced methylphenidate concentrations occurring during the use of carbamazepine concurrently. The mechanism of the interaction is not clear as methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body. Interactions with other potent enzyme inducers have not been reported. Monitor for any changes in therapeutic effectiveness of either drug.
Carbidopa; Levodopa; Entacapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Carteolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Carvedilol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Celecoxib; Tramadol: (Moderate) Concurrent use of tramadol and methylphenidate derivatives might increase the risk for serotonin syndrome. If concomitant use is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue 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. There are also postmarketing reports of serotonin syndrome during concurrent use of methylphenidate or methylphenidate derivatives with other serotonergic medications.
Chlordiazepoxide; Amitriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Chlorothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Chlorpheniramine; Codeine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives 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; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Chlorpheniramine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives 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) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Citalopram: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Clevidipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Clomipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Clonidine: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
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 methylphenidate or its derivatives 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 methylphenidate or its derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives 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 methylphenidate or its derivatives 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. (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Codeine; Promethazine: (Moderate) If concomitant use of codeine and methylphenidate or its derivatives 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.
COMT inhibitors: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Dapagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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.
Desflurane: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
Desipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Desvenlafaxine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Dextromethorphan; Bupropion: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Diazoxide: (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.
Diltiazem: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
dopamine agonists: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Dopamine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dorzolamide; Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Doxazosin: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Doxepin: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
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.
Droxidopa: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dulaglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Duloxetine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Empagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Entacapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Ephedrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Ephedrine; Guaifenesin: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Eplerenone: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as eplerenone.
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: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Ergotamine; Caffeine: (Moderate) Caffeine is a CNS stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Avoid excessive caffeine intake during use of methylphenidate or its derivatives. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Ertugliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Esketamine: (Major) Closely monitor blood pressure during concomitant use of esketamine and methylphenidate or its derivatives. Coadministration of psychostimulants, such as methylphenidates, with esketamine may increase blood pressure, including the possibility of hypertensive crisis.
Esmolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Ethacrynic Acid: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Exenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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.
Felodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Fenfluramine: (Moderate) Use fenfluramine and methylphenidate derivatives 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.
Fenoldopam: (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.
Fentanyl: (Moderate) If concomitant use of fentanyl and methylphenidate or its derivatives 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) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
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) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Fosinopril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Furosemide: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Glimepiride: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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.
Green Tea: (Moderate) The CNS stimulant effects of methylphenidate derivatives can be additive when used concurrently with most other psychostimulants, such as caffeine, including foods, herbal or dietary supplement products containing high amounts of caffeine like green tea. The combination of methylphenidate derivatives with other CNS stimulants may increase the incidence of side effects. Patients should avoid excessive caffeine intake, and observe for signs of nervousness, irritability, insomnia, tremor, arrhythmias, or other stimulant-related problems.
Guaifenesin; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Guanfacine: (Moderate) Psychostimulants, such as methylphenidate and its derivatives, 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 methylphenidate and its derivatives in the treatment of attention deficit hyperactivity disorder (ADHD). Pharmacokinetic studies reveal that guanfacine does not influence methylphenidate pharmacokinetics and methylphenidate does not affect guanfacine pharmacokinetics. No dosage adjustments are required when used together. Patients should be monitored for heart rate, blood pressure, and for sedation during ADHD treatment.
Halogenated Anesthetics: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
Homatropine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives 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: (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.
Hydralazine; Isosorbide Dinitrate, ISDN: (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. (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.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Hydrocodone: (Moderate) If concomitant use of hydrocodone and methylphenidate derivatives 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 methylphenidate derivatives 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 methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Ibuprofen; Oxycodone: (Moderate) If concomitant use of oxycodone and methylphenidate derivatives 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.
Imipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Incretin Mimetics: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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; 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) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as indapamide. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Insulin Aspart: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 Aspart; Insulin Aspart Protamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 Degludec: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 Degludec; Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 Detemir: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 Glulisine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 Lispro: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 Lispro; Insulin Lispro Protamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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, Inhaled: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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.
Iodixanol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioflupane I 123: (Major) Hold methylphenidate and methylphenidate derivatives for 7 days, or at least 5 medication half-lives, prior to performing dopamine transporter (DAT) imaging with radiolabeled ioflupane. Methylphenidate binds to the dopamine transporter which may interfere with striatal tracer binding and increase the risk for a false-positive scan.
Iohexol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Irbesartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Isocarboxazid: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Isoflurane: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
Isophane Insulin (NPH): (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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.
Isosorbide Dinitrate, ISDN: (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.
Isosorbide Mononitrate: (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.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isradipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Ketamine: (Moderate) Closely monitor vital signs when ketamine and methylphenidate derivatives are coadministered; consider dose adjustment individualized to the patient's clinical situation. Methylphenidate derivatives may enhance the sympathomimetic effects of ketamine.
Labetalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylphenidate derivatives. 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.
Levamlodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Levobunolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Levomilnacipran: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Levorphanol: (Moderate) If concomitant use of levorphanol and methylphenidate derivatives 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) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Lidocaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Linagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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.
Linagliptin; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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: (Major) Psychostimulants, such as methylphenidate derivatives, exhibit sympathomimetic actions and should be avoided with other drugs, such as linezolid, that enhance the pressor response of sympathomimetic agents. A clinically significant rise in systolic blood pressure is possible. In addition, serotonin syndrome has been reported during the concurrent use of linezolid, a non-selective monoamine oxidase inhibitor (MAOI), and medications that enhance central serotonergic activity. Monoamine oxidase (MAO) is the enzyme responsible for the degradation of norepinephrine, dopamine, and serotonin. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Liothyronine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Lithium: (Moderate) Monitor for serotonin syndrome, particularly during lithium initiation, during concomitant methylphenidate use. If serotonin syndrome occurs, consider discontinuation of lithium and/or methylphenidate.
Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Losartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
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.
Macitentan; Tadalafil: (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.
Maprotiline: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Meperidine: (Moderate) If concomitant use of meperidine and methylphenidate derivatives 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.
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; Saxagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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 methylphenidate derivatives 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.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Methyldopa: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including methyldopa. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate derivatives may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and methylphenidate increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by the rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Metoclopramide: (Moderate) In theory, metoclopramide and methylphenidate derivatives may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Patients receiving this combination should be monitored for loss of effectiveness of either agent. Methylphenidate derivatives blocks central dopamine reuptake, which increases central dopaminergic functioning, while metoclopramide is a dopamine antagonist.
Metolazone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Metoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Midodrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Miglitol: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Milnacipran: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Minoxidil: (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.
Mirtazapine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and mirtazapine.
Modafinil: (Major) The use of modafinil with other psychostimulants, including methylphenidate or its derivatives, 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. Single dose studies of methylphenidate combined with modafinil noted that the rate of absorption of modafinil was delayed up to one hour by the presence of methylphenidate; no changes occurred in the metabolism and extent of absorption of either medication.
Moexipril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Monoamine oxidase inhibitors: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Morphine: (Moderate) If concomitant use of morphine and methylphenidate derivatives 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 methylphenidate derivatives 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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nalbuphine: (Moderate) If concomitant use of nalbuphine and methylphenidate derivatives 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.
Nateglinide: (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.
Nebivolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nebivolol; Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nefazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and nefazodone. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Nicardipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
NIFEdipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Nimodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Nisoldipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
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.
Nitroglycerin: (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.
Nitroprusside: (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.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Methylphenidate derivatives should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Norepinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Nortriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Olanzapine; Fluoxetine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Oliceridine: (Moderate) If concomitant use of oliceridine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olmesartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Opicapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Oxycodone: (Moderate) If concomitant use of oxycodone and methylphenidate derivatives 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 methylphenidate derivatives 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: (Contraindicated) Coadministration of ozanimod with methylphenidate derivatives is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of methylphenidate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as methylphenidate may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Methylphenidate derivatives may 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) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Perindopril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Perindopril; Amlodipine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Perphenazine; Amitriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Phenelzine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Phenobarbital: (Moderate) Psychostimulants, such as methylphenidate derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as phenobarbital. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenobarbital. More frequent monitoring of phenobarbital concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on phenobarbital concentrations is not clear; methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body, and appears to have no known inhibitory effect on hepatic enzymes.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Psychostimulants, such as methylphenidate derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as phenobarbital. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenobarbital. More frequent monitoring of phenobarbital concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on phenobarbital concentrations is not clear; methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body, and appears to have no known inhibitory effect on hepatic enzymes.
Phenoxybenzamine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Phentolamine: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Pimozide: (Major) Pimozide should not be used in patients taking medicines that may, themselves, cause motor and phonic tics (e.g., methylphenidate) until such patients have been withdrawn from these drugs to determine whether or not the drugs, rather than Tourette's Disorder, are responsible for the tics. Once this issue is excluded, use together may proceed with caution.
Pindolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Pioglitazone; Glimepiride: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Pioglitazone; Metformin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Pramipexole: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
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: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Prilocaine; Epinephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Primidone: (Moderate) Psychostimulants, such as methylphenidate derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as primidone. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of primidone, which is metabolized to phenobarbital. More frequent monitoring of drug concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on primidone concentrations is not clear; methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body, and appears to have no known inhibitory effect on hepatic enzymes.
Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
Promethazine; Phenylephrine: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Propranolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Protriptyline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Quinapril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Ramipril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
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.
Regular Insulin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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.
Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with methylphenidate derivatives. 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.
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.
Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Risperidone: (Moderate) Monitor for extrapyramidal symptoms (EPS) with concomitant use of risperidone and methylphenidate derivatives. Postmarketing cases of extrapyramidal symptoms (dystonia and dyskinesia) have been reported in patients when there was a change in dosage of either medication (increase or decrease in dosage) as well as with the initiation or discontinuation of either or both medications.
Ropinirole: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Rosiglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sacubitril; Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Safinamide: (Contraindicated) Safinamide, a selective monoamine oxidase-B inhibitor, is contraindicated for use with methylphenidate and its derivatives due to the risk of serotonin syndrome and 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 methylphenidate. Safinamide can cause hypertension or exacerbate existing hypertension, particularly at daily dosages exceeding those recommended by the manufacturer.
Saxagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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.
Selective serotonin reuptake inhibitors: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Selegiline: (Contraindicated) The product labels for methylphenidate and its derivatives contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. Methylphenidate derivatives should not be used concurrently with selegiline or within 14 days before or after selegiline use.
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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Sertraline: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Sevoflurane: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
SGLT2 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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.
Sitagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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.
Sodium Oxybate: (Moderate) The stimulant effects of methylphenidate derivatives can be additive when used concurrently with other psychostimulants, such as sodium oxybate. The combination may increase the incidence of side effects; if these combinations cannot be avoided the patient should be closely observed for signs of nervousness, irritability, insomnia, arrhythmias, or other stimulant-related problems. 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. Note that CNS stimulants, including methylphenidate, 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 methylphenidate derivatives, 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.
Sotagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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.
Sotalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Spironolactone: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
St. John's Wort, Hypericum perforatum: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering methylphenidate derivatives and St. John's Wort. There are rare reports of serotonin syndrome occurring during use of other serotonergicagents and methylphenidate or its derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with methylphenidate derivatives. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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 methylphenidate derivatives 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: (Moderate) Psychostimulants, such as methylphenidate and its derivatives, exhibit sympathomimetic actions and may interact with other drugs, such as tedizolid, that enhance the pressor response of sympathomimetic agents. In addition, serotonin syndrome has been reported during the concurrent use of linezolid, which is structurally related to tedizolid, and medications that enhance central serotonergic activity. Tedizolid inhibits monoamine oxidase (MAO), the enzyme responsible for the degradation of norepinephrine, dopamine, and serotonin. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Telmisartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Telmisartan; Amlodipine: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Terazosin: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with sympathomimetics can produce excessive stimulation manifested by skeletal muscle activity, agitation, and hyperactivity.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Thiazolidinediones: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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.
Thyroid hormones: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Tirzepatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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.
Tolcapone: (Minor) Due to their pharmacologic actions, it is thought that increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and COMT inhibitors. Be alert for any dopamine-related side effects such as nausea, reduced appetite, tremor, or changes in moods or behaviors.
Torsemide: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Tramadol: (Moderate) Concurrent use of tramadol and methylphenidate derivatives might increase the risk for serotonin syndrome. If concomitant use is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue 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. There are also postmarketing reports of serotonin syndrome during concurrent use of methylphenidate or methylphenidate derivatives with other serotonergic medications.
Tramadol; Acetaminophen: (Moderate) Concurrent use of tramadol and methylphenidate derivatives might increase the risk for serotonin syndrome. If concomitant use is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue 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. There are also postmarketing reports of serotonin syndrome during concurrent use of methylphenidate or methylphenidate derivatives with other serotonergic medications.
Trandolapril: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Trandolapril; Verapamil: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors. (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Tranylcypromine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
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: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Tricyclic antidepressants: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Trimipramine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and tricyclic antidepressants (TCAs). There are postmarketing reports of serotonin syndrome occurring during use of methylphenidate derivatives and other serotonergic medications. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Valsartan: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
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.
Vasopressin, ADH: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Vasopressors: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Venlafaxine: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and serotonin norepinephrine reuptake inhibitors (SNRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy after ingesting methylphenidate with an SNRI. It is unclear if the reaction was the result of a drug interaction. Monitor patients for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Verapamil: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Vilazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and vilazodone. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored closely for toxicity. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate derivatives and vortioxetine. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving methylphenidate derivatives with vortioxetine should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Warfarin: (Moderate) A dose adjustment of warfarin and more frequent INR monitoring may be required when initiating or discontinuing methylphenidate derivatives. Case reports suggest a potential interaction between methylphenidate derivatives and coumarin anticoagulants. Human pharmacologic studies have shown that methylphenidate derivatives may inhibit the metabolism of warfarin. The mechanism of the potential interaction is not clear. A dose adjustment of warfarin and more frequent monitoring of the INR may be required when initiating or discontinuing methylphenidate derivatives.
Dexmethylphenidate is a central nervous system stimulant. The drug exhibits activity similar to that of the amphetamines, although the underlying pharmacology for these two drug classes may differ. Dexmethylphenidate, the more pharmacologically active enantiomer of the d- and l-enantiomers, is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. This action is in contrast to the amphetamines and cocaine, which increase catecholamine release as a primary mechanism. There is some evidence that the alteration of dopamine transport systems by dexmethylphenidate may indirectly augment the action of serotonin, but further pharmacologic research is needed. The main sites of CNS activity appear to be the brain stem arousal system and the cerebral cortex, including the subcortical structures of the thalamus. Dexmethylphenidate-induced CNS stimulation produces a decreased sense of fatigue, an increase in motor activity and mental alertness, mild euphoria, and brighter spirits. A mild anorexic effect may occur. Unlike the amphetamines and cocaine, physical dependence is infrequent with normal clinical use at therapeutic doses. Chronic use of dexmethylphenidate may lead to tolerance and psychic dependence, similar to other psychostimulants. Psychic dependence and addiction are more likely with parenteral or inhalational abuse, and are usually noted with illicit street use of the racemic drug (e.g., methylphenidate).
-Peripheral actions: In the periphery, the sympathomimetic actions of dexmethylphenidate are minimal at therapeutic doses, and are less than those of the amphetamines or cocaine. Because dexmethylphenidate slowly blocks the dopamine-transport proteins, the drug appears less likely than the amphetamines or cocaine to increase systolic and diastolic blood pressure or cause respiratory stimulation. At higher dosages and in overdose, heart rate may increase or reflexly decrease in response to blood pressure; cardiac arrhythmias may occur secondary to increased sympathomimetic effects.
-Actions in ADHD: The mechanism(s) of action of the treatment of mental and behavioral conditions in ADHD are not established. Improved attention spans, decreased distractibility, increased ability to follow directions or complete tasks, and decreased impulsivity and aggression have been noted when stimulants are prescribed for the treatment of ADHD. Current research suggests that the modulation of serotonergic pathways via changes in dopamine transport may contribute to the calming effects in the treatment of this disorder, but precise pharmacologic mechanisms have yet to be elucidated.
Dexmethylphenidate is administered orally. Plasma protein binding of the d-enantiomer is not known; however, racemic methylphenidate is approximately 12% to 15% protein bound. Volume of distribution (Vd) is 2.65 +/- 1.11 L/kg. Dexmethylphenidate is metabolized in the liver via de-esterification to the primary metabolite d-alpha-phenyl-piperidine acetic acid (d-PPA, d-ritalinic acid), which has little or no pharmacological activity. There is no in vivo interconversion to the l-threo-enantiomer. Only small quantities (less than 0.5%) of unchanged drug are eliminated in the urine, most of the dose (80%) is renally excreted as the inactive metabolite. The mean elimination half-life in adults is approximately 3 hours.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Oral Route
Dexmethylphenidate is well absorbed after oral administration; however, mean bioavailability is only 22% to 25% due to first pass metabolism. Plasma concentrations decline exponentially after oral administration. Both formulations, when given to pediatric patients and adults as a single dose (immediate-release: 2.5 mg, 5 mg, or 10 mg; extended-release: 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg), result in a Cmax and AUC proportional to the dose given. Plasma dexmethylphenidate concentrations are comparable to those achieved after a single racemic methylphenidate dose given in twice the total mg amount (equimolar with respect to dexmethylphenidate). Pharmacokinetic parameters are similar with single and repeat dosing indicating no significant drug accumulation.
Immediate-release formulations
Immediate-release dexmethylphenidate is readily absorbed, reaching maximum concentrations approximately 1 to 1.5 hours after administration (fasted state). When given with a high fat meal, Tmax increases from 1.5 hours to 2.9 hours; however, Cmax and AUC are comparable in fasted and non-fasted states.
Extended-release formulations
Extended-release dexmethylphenidate produces a biphasic pharmacokinetic profile to provide day-long medication availability with once daily administration. Using Spheroidal Oral Drug Absorption (SODAS) technology, the capsules contain the drug in both rapid-release and enteric-coated delayed-release beads that allow for 50% of the dose to be released rapidly and 50% to be released approximately 4 hours later. Extended-release dexmethylphenidate is readily absorbed, with an early Tmax of 1.5 hours (range: 1 to 4 hours) and a late Tmax of 6.5 hours (range: 4.5 to 7 hours) after administration. Mean time to interpeak minimum (Tmin) is slightly shorter and time to late Tmax is slightly longer for the extended-release product given once daily compared to the immediate-release product (2 doses given 4 hours apart); ranges observed are greater with the extended-release product. In addition, extended-release dexmethylphenidate given once daily exhibits a lower late Cmax and higher interpeak Cmin, resulting in fewer fluctuations in plasma concentrations compared to twice daily dosing with the immediate-release tablet.
The effects of food on dexmethylphenidate extended-release capsules have not been studied. However, the effects of food on extended-release methylphenidate (Ritalin LA) capsules, also formulated with SODAS technology, have been studied and, per FDA-approved labeling, are applicable to extended-release dexmethylphenidate. When the drug is given with a high-fat meal, absorption is delayed, resulting in variable delays in initial Tmax, interpeak Tmin, and late Tmax. The initial Cmax is unaffected, but late Cmax is decreased by approximately 25%. There is no evidence of dose dumping in the presence or absence of food. When administered with applesauce, the pharmacokinetic profile does not differ from that of the fasted state.
-Special Populations
Hepatic Impairment
Dexmethylphenidate pharmacokinetic parameters have not been evaluated in the presence of hepatic dysfunction.
Renal Impairment
Dexmethylphenidate pharmacokinetic parameters have not been evaluated in the presence of renal dysfunction. Because very little unchanged drug is excreted in the urine, renal insufficiency is not expected to appreciably alter the pharmacokinetic profile.
Pediatrics
Children
Cmax was similar, and AUC was somewhat lower in children (age 6 to 12 years) compared to adults after single dose administration of immediate-release dexmethylphenidate during clinical trials. The pharmacokinetic profile of extended-release dexmethylphenidate has not been studied in the pediatric population. However, a similar formulation of racemic methylphenidate (Ritalin LA), when studied in children 7 to 12 years of age (n = 18), demonstrated a similar initial Tmax compared to adults. Time to interpeak minimum (Tmin) and late Tmax was delayed and more variable in children compared to adults. The mean elimination half-life in pediatric patients is approximately 2 to 3 hours, which is slightly shorter than in adults.
Gender Differences
In a single dose study conducted in adults, mean AUC (adjusted for body weight) was 25% to 35% higher in females (n = 6) compared to males (n = 9) after a single 20 mg dose of immediate-release dexmethylphenidate. Tmax and half-life were comparable for both sexes. Additionally, initial Cmax (adjusted for body weight) was 45% higher in women who received extended-release dexmethylphenidate. Interpeak Cmin and late Cmax also tended to be slightly higher in women, although the difference was not clinically significant.