CONTRAINDICATIONS / PRECAUTIONS
General Information
Methylphenidate is contraindicated in patients with known hypersensitivity to methylphenidate or any component of this product. Cross-sensitivity with dexmethylphenidate should be expected. Life-threatening hypersensitivity reactions, including angioedema and anaphylaxis, have been reported during methylphenidate administration. The use of transdermal methylphenidate may lead to contact sensitization. If contact sensitization is suspected, the methylphenidate patch should be discontinued. Patients who have previously developed contact dermatitis with transdermal methylphenidate may also be sensitized to oral methylphenidate and should be initiated on oral therapy under close supervision. After initial development of contact dermatitis from the methylphenidate patch, re-exposure to the drug by other routes of administration may result in systemic sensitization or other systemic reactions. Symptoms may include a flare-up of previous dermatitis, generalized skin eruptions to previously unaffected skin, headache, fever, malaise, arthralgia, diarrhea, or vomiting. Some patients who develop sensitization to the patch may not be able to use the oral products. Patients should alternate hip application sites each day to help prevent sensitization.[32121]
Abrupt discontinuation
Abrupt discontinuation after chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.[28518] [33387] Drug 'holidays', the temporary discontinuation of the drug during weekends, holidays, summer vacations, etc., is usually not associated with drug withdrawal symptoms, but such holidays are typically reserved for those patients with well-controlled ADHD symptoms.
Anxiety, bipolar disorder, depression, mania, psychosis, schizophrenia, suicidal ideation
Some methylphenidate formulations, including immediate-release chewable tablets, transdermal patch, immediate-release oral solution, and some extended-release capsules and tablets are contraindicated by the manufacturers in patients with marked anxiety, tension, or agitation because the drug can aggravate these conditions. Other methylphenidate products have no contraindications or precautions for these conditions in their product labeling. Use stimulants with caution in those with bipolar disorder and/or mania due to the potential for manic episodes to occur. Prior to initiating treatment with methylphenidate, screen patients for risk factors for bipolar disorder or manic episodes (mania), such as comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression. Due to its toxic effects in overdose, only use methylphenidate in those with major depression or suicidal ideation when absolutely necessary. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and postmarketing experience with attention-deficit hyperactivity disorder (ADHD) medications. Although causality has not been established and these behaviors may be inherent to ADHD, close monitoring is recommended. Advise patients and their caregivers to promptly report any changes in mood or behavior. If suicide-related events emerge during treatment, consider dose reduction or drug discontinuation, especially if symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. In patients with pre-existing psychosis (e.g., schizophrenia), methylphenidate can exacerbate behavioral disturbances and thought disorders. New onset psychotic symptoms may occur in individuals without a prior history of psychosis. If such symptoms occur, consider discontinuing treatment.[28405] [28518] [31289] [32121] [33387] [34475] [43863] [45983] [56750] [56765] [56766] [64025]
Tics, Tourette's syndrome
Some methylphenidate products, including immediate-release chewable tablets, transdermal patch, immediate-release oral solution, and some extended-release capsules and tablets are contraindicated in patients with motor tics, Tourette's syndrome, or a family history of Tourette's syndrome because the drug may precipitate motor or phonetic tics. Other dosage forms have no contraindications or precautions related to motor tics or Tourette's syndrome in their product labeling.[28518] [31289] [32121] [33387] [34475] [45983] [51955] [59540] [60401] [62034]
Glaucoma
Some methylphenidate products, including immediate-release chewable tablets, transdermal patch, immediate-release oral solution, and some extended-release capsules and tablets are contraindicated in patients with glaucoma, due to the ability of the drug to increase sympathetic stimulation and to raise intraocular pressure. Other dosage forms have no contraindications or precautions related to glaucoma in their product labeling.[28518] [31289] [32121] [33387] [34475] [51955] [59540] [60401] [62034]
Alcoholism, substance abuse
Methylphenidate has a high potential for abuse. Caution is recommended in patients with a known history of substance abuse, including alcoholism. Assess the risk of abuse prior to prescribing and monitor for signs of abuse while on therapy. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Additionally, educate patients and their families about abuse and proper storage and disposal of CNS stimulants. Misuse of stimulants may cause serious cardiovascular adverse reactions and has been associated with sudden death. Symptoms of chronic stimulant abuse may include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders, particularly with parenteral or inhalational abuse.[31287] [33387] [34475] [55116]
Hypertension, tachycardia, ventricular arrhythmias
Methylphenidate should be used with caution in patients with cardiac conditions (i.e., hypertension, tachycardia, ventricular arrhythmias) that would be expected to deteriorate from significant increases in blood pressure or heart rate. Stimulant medications cause a modest increase in average blood pressure (approximately 2 to 4 mmHg) and average heart rate (approximately 3 to 6 bpm); however, some individuals may have larger increases. Monitor all patients for hypertension and tachycardia. Specifically, heart rate and blood pressure measurements should be obtained at baseline, after dosage increases, and periodically throughout methylphenidate therapy. The manufacturer of Metadate CD and Metadate ER considers severe hypertension as a contraindication for use.[28518] [34206] [34475] [43863]
Acute myocardial infarction, angina, aortic stenosis, arteriosclerosis, cardiac arrhythmias, cardiac disease, cardiomyopathy, cerebrovascular disease, congenital heart disease, coronary artery disease, heart failure, myocardial infarction, prosthetic heart valves, stroke, valvular heart disease, ventricular dysfunction
Methylphenidate generally should not be used in patients with serious structural cardiac abnormalities, aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, ventricular dysfunction or heart failure, serious cardiac arrhythmias, coronary artery disease, cerebrovascular disease, advanced arteriosclerosis, or other serious cardiac problems that may make them more vulnerable to the noradrenergic effects of methylphenidate. The labels for Metadate CD and Metadate ER list angina pectoris, cardiac arrhythmias, heart failure, and acute myocardial infarction as contraindications for use. Sudden death, myocardial infarction, and stroke have occurred in adults receiving standard dosages of stimulants. Sudden death has also been associated with stimulant use at usual doses in children and adolescents with structural congenital heart disease or other serious cardiac disease. However, a retrospective cohort study including over 1.2 million children and young adults 2 to 24 years of age did not find an increased risk of serious cardiovascular events (sudden cardiac death, acute myocardial infarction, or stroke) in current users of drugs for the treatment of attention deficit hyperactivity disorder (ADHD) compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31 to 1.85). This data is supported by results from another large population-based retrospective cohort study (patients aged 3 to 18 years) that found no increase in short-term risk of severe cardiac events in stimulant users vs. nonusers (adjusted odds ratio 0.62; 95% CI 0.27 to 1.44). Unlike other trials, this second study also included high risk patients (e.g., patients with malignancy, HIV, congenital heart disease, or cardiomyopathy); the odds ratio in the high risk group was 1.02 (95% CI 0.28 to 3.69). The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. 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 (IRR 1.33; 95% CI 0.9 to 1.98), but risk was elevated after the first week of treatment through week 8. An increased risk of hypertension, stroke, or heart failure was not observed. The American Heart Association (AHA) states that it is reasonable to consider the use of these medications in pediatric patients with congenital heart disease without current hemodynamic or arrhythmic concerns or congenital heart disease that is considered stable by the patient's pediatric cardiologist, unless the cardiologist has specific concerns. However, these patients should be closely monitored and treatment discontinuation should be considered if the patient develops any of the following conditions: heart condition associated with sudden cardiac death (SCD), arrhythmia requiring cardiopulmonary resuscitation, direct current cardioversion/defibrillation or overdrive pacing, arrhythmia associated with SCD, any clinically significant arrhythmia that is not treated or controlled, QTc on electrocardiogram (ECG) more than 0.46 sec, or heart rate or blood pressure more than 2 SD above the mean for age. All patients being considered for treatment with stimulant medications should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmias, and a physical exam to assess for the presence of cardiac disease. If cardiac disease is suspected, further cardiac evaluation including an ECG and echocardiogram is warranted. For pediatric patients, the AHA states that it is reasonable to obtain a baseline ECG as a part of the initial evaluation. If a child or adolescent has any significant findings on physical examination, ECG, or family history, consult a pediatric cardiologist before initiating the stimulant medication.[28518] [34206] [34475] [43863] [46635] [46636] [52279] [60878]
Growth inhibition
The potential for growth inhibition in pediatric patients should be monitored during stimulant therapy. Monitor height and weight parameters relative to age at treatment initiation and periodically thereafter (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. Data obtained on the effects of methylphenidate on growth suppression in children 7 to 10 years of age suggested that regularly medicated children (7 days/week) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years. Data are inadequate to determine whether chronic use of stimulants causes long-term growth inhibition. Although data are limited, available studies do not indicate that stimulant use compromises the attainment of normal adult height and weight in most children. Growth rebound has been observed after stimulant discontinuation, and some experts recommend the use of drug holidays to allow growth to 'catch-up'. However, drug holidays are typically reserved for children with well-controlled attention-deficit hyperactivity disorder (ADHD) symptoms and are of unproved value in limiting growth suppression.[28518] [31578] [31592] [45900] [55378] [55379] [55380] [55381] [55382] [55383] [58775]
Hyperthyroidism, thyrotoxicosis
Methylphenidate use in patients with hyperthyroidism or thyrotoxicosis is contraindicated by the manufacturer of Metadate CD and Metadate ER, as sympathomimetic stimulation may induce cardiac arrhythmias or other side effects. There are no contraindications or precautions related to hyperthyroidism or thyrotoxicosis in the product labeling of other methylphenidate formulations.[28518] [34475] [43863]
Priapism
In rare instances, stimulant medications may cause prolonged and sometimes painful erections (priapism). All male patients and their caregivers should be counseled on the signs and symptoms of priapism and the importance of seeking immediate medical attention if an erection lasting longer than 4 hours occurs. 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 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.[33387] [56554]
Neonates, pregnancy
The safety of methylphenidate, a CNS stimulant, during human pregnancy has not been established. There may be risks to the fetus associated with the use of CNS stimulants during pregnancy. Because stimulants cause vasoconstriction, they may decrease placental perfusion. However, limited published studies and postmarketing reports on the use of methylphenidate during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. 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. It is unclear what effect, if any, a CNS stimulant such as methylphenidate would have on the developing fetal brain. There is a pregnancy registry that monitors pregnancy outcomes in women exposed to ADHD medications, including methylphenidate, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or by visiting the worldwide web at https://womensmentalhealth.org/adhd-medications/. The effects of methylphenidate during labor and delivery are unknown; however, there are reports of premature delivery and low birth weight infants who have been born to mothers dependent on amphetamines.
Breast-feeding
The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for methylphenidate and any potential adverse effects on the breastfed infant from methylphenidate or from the underlying maternal condition. Methylphenidate has a low molecular weight and is excreted in human breast milk. Limited data from published literature have indicate an approximate infant dose of 0.16% to 0.7% of the maternal weight-adjusted dosage 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. Based on data from 2 breast-feeding mothers, one receiving 15 mg/day and one receiving 80 mg/day, the estimated infant dose ranged from 0.38 mcg/kg/day to 2.3 mcg/kg/day or 0.16% to 0.2% of the maternal weight-adjusted dose. One of the infants was a 6.5 month old who received most of his nutrition from breast milk and the other an 11 month old who was only sporadically nursing; the mothers reported no adverse events. Although methylphenidate 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 methylphenidate, the nursing infant should be monitored for signs of central nervous system hyperactivity, including 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.
Driving or operating machinery
The use of methylphenidate may cause dizziness, mask signs of fatigue or the need for rest, or impair the ability of a patient to participate in activities that require mental alertness. Patients should not use methylphenidate for the prevention or treatment of normal fatigue states. Patients should not perform such tasks, including driving or operating machinery, until they are aware of how this medication affects them.
Heating pad
All patients should be advised to avoid exposing the methylphenidate patch application site to direct external heat sources (i.e., a heating pad, electric blanket, heated water bed) while wearing the patch. There is a potential for temperature-dependent increases in methylphenidate release of greater than 2-fold from the patch when there is extreme ambient temperature increase at the site of application.[32121]
Seizure disorder, seizures
Methylphenidate may lower the seizure threshold and should be used cautiously in patients with a history of a seizure disorder or EEG abnormalities. Rarely, seizures have occurred in patients with no prior history or EEG evidence of seizure. Concomitant use of methylphenidate and anticonvulsants have not been established. The product labeling for some formulations of methylphenidate recommends discontinuing methylphenidate if seizures occur; the product labeling for other methylphenidate formulations do not contain a precaution for patients with a history of seizures.[28518] [32121] [33387] [34475]
Cystic fibrosis, dysphagia, esophageal stricture, GI obstruction, ileus, peritonitis
There is a potential for Concerta tablets to cause GI obstruction in susceptible patients. The Concerta extended-release tablet is nondeformable and does not change shape when passing through the GI tract. Use with caution in patients who have a history of severe GI narrowing, such as those patients with inflammatory bowel disease, short gut syndrome, history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, diverticular disease, or ileus. Patients with dysphagia, esophageal motility disorders, or esophageal stricture may not be able to swallow extended-release methylphenidate dosage forms whole and may be at risk for GI obstruction.
Anorexia nervosa, bulimia nervosa, obesity treatment
Methylphenidate is not approved by the FDA 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.[56717]
Geriatric
The safety and efficacy of methylphenidate have not been specifically assessed in geriatric patients. However, 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 methylphenidate; 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.
MAOI therapy
Methylphenidate is contraindicated in patients who have received MAOI therapy within the past 14 days because of the possibility of precipitating a hypertensive crisis.
Peripheral vascular disease, Raynaud's phenomenon
Stimulant medications are associated with peripheral vasculopathy, including Raynaud's phenomenon. Worsening of peripheral vascular disease is possible. Effects on circulation have been observed with therapeutic doses at different times throughout therapy in all age groups. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor all patients for digital changes during treatment with stimulant medications, especially those with pre-existing circulation problems. Instruct patients to seek immediate medical attention if any new digital numbness, pain, skin discoloration, or temperature sensitivity occur, or if unexplained wounds appear on their fingers or toes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
Chemical leukoderma, skin hypopigmentation, vitiligo
Chemical leukoderma, a condition that causes the skin to lose color from repeated exposure to specific chemical compounds, may occur with use of the methylphenidate patch. The condition is not physically harmful, but it is disfiguring and is thought to be irreversible, which may cause emotional distress. The areas of skin color loss described with the methylphenidate patch have ranged up to 8 inches in diameter, with a time of onset ranging from 2 months to 4 years after starting the patch. Skin hypopigmentation has occurred under and around the patch, and less frequently on parts of the body where the patch was never applied. Chemical leukoderma can mimic the appearance of vitiligo, particularly at remote sites of skin hypopigmentation. Individuals with a history of vitiligo and/or a family history of vitiligo may be more at risk. Patients and caregivers should be advised to watch for new areas of lighter skin, especially under the drug patch, and immediately report these changes to their health care providers. Alternative treatment should be considered in patients who experience these skin changes.]
Phenylketonuria
Methylphenidate chewable tablets (e.g., Methylin, QuilliChew ER) contain aspartame. Phenylalanine is a component of aspartame and can be harmful to patients with phenylketonuria (PKU). Before prescribing these formulations in patients with PKU, consider the combined daily amount of phenylalanine from all sources.
Hereditary fructose intolerance
The Metadate CD product contains sucrose. The manufacturer of Metadate CD considers its product contraindicated in patients with hereditary fructose intolerance, glucose-galactose malabsorption, and sucrase-isomaltase insufficiency.
Surgery
The use of inhalational anesthetics during surgery may sensitize the cardiovascular system to the effects of methylphenidate. There may be a risk of sudden blood pressure increases during administration of halogenated anesthetics.[28325] [30143] The FDA-approved product labeling for Metadate CD and Metadate ER states that these products are contraindicated on the day of surgery due to the risk of sudden blood pressure increases during administration of halogenated anesthetics. The product labeling for some other formulations of methylphenidate recommends avoiding administration of methylphenidate on the day of surgery in patients receiving halogenated anesthetics; other methylphenidate formulations do not contain a precaution for patients on the day of surgery.[28518] [31289] [34475] [43863] [59540]
Tartrazine dye hypersensitivity
Methylphenidate extended-release (Adhansia XR) 45 mg oral capsules contain tartrazine dye (FD&C Yellow No. 5) and can precipitate bronchial asthma or other allergic reactions in patients with tartrazine dye hypersensitivity.[63983]
DRUG INTERACTIONS
Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acebutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) 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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Butalbital; Caffeine: (Moderate) 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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) 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. 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. 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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) 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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) 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. 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 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; Phenyltoloxamine: (Moderate) Methylphenidate 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; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate 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 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 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.
Albiglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Alpha-blockers: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate 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.
Aluminum Hydroxide: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Aluminum Hydroxide; Magnesium Carbonate: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Aluminum Hydroxide; Magnesium Hydroxide: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Aluminum Hydroxide; Magnesium Trisilicate: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Amantadine: (Moderate) Use of amantadine with methylphenidate, a CNS stimulant, requires careful observation. Coadministration may increase the risk of stimulant effects, such as nervousness, irritability, insomnia, tremor, seizures, or cardiac arrhythmias.
Ambrisentan: (Moderate) Methylphenidate can reduce the hypotensive effect of antihypertensive agents. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with methylphenidate 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 may increase the risk of seizures.
Amiloride: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
Amiloride; Hydrochlorothiazide, HCTZ: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
Amitriptyline: (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Amitriptyline; Chlordiazepoxide: (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Amoxapine: (Moderate) Both methylphenidate 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.
Amoxicillin; Clarithromycin; Lansoprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Angiotensin II receptor antagonists: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as angiotensin II receptor antagonists.
Angiotensin-converting enzyme inhibitors: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Antacids: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Apomorphine: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor 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.
Aripiprazole: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Armodafinil: (Major) The use of armodafinil with other psychostimulants, including methylphenidate, 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.
Asenapine: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) 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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) 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. 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. 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; Citric Acid; Sodium Bicarbonate: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Aspirin, ASA; Omeprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Atenolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Atenolol; Chlorthalidone: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Atomoxetine: (Moderate) Use atomoxetine and methylphenidate together with caution and monitor for additive effects. Monitor heart rate and blood pressure, as well as for any changes in moods or behavior. Pulse and blood pressure should be measured at baseline, following any dose increases, and periodically while on therapy to detect possible clinically important increases. Coadministration of methylphenidate and atomoxetine did not increase the cardiovascular effects seen with administration of methylphenidate alone during clinical trials of atomoxetine. However, methylphenidate has sympathomimetic effects and atomoxetine may increase the blood pressure and heart rate.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate 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.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Psychostimulants, such as methylphenidate, 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.
atypical antipsychotic: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Psychostimulants, such as methylphenidate, 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.
Bendroflumethiazide; Nadolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate 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: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Betaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
Bisoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Bosentan: (Major) Avoid use of sympathomimetic agents with bosentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including bosentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Brexpiprazole: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Brimonidine; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Bromocriptine: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor 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; Carbetapentane; Phenylephrine: (Moderate) Methylphenidate 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.
Bupropion: (Major) Drugs which may lower the seizure threshold, such as methylphenidate, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored.
Bupropion; Naltrexone: (Major) Drugs which may lower the seizure threshold, such as methylphenidate, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored.
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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Caffeine; Ergotamine: (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. Excessive caffeine ingestion (via medicines, foods like chocolate, dietary supplements, or beverages including coffee, green tea, other teas, colas) may contribute to side effects like nervousness, irritability, nausea, insomnia, or tremor. Patients should avoid medications and dietary supplements which contain high amounts of caffeine.
Calcium Carbonate: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Because the modified release characteristics are pH-dependent, it is possible that the administration of antacids or other acid suppressants could alter the release of extended-release methylphenidate. Patients receiving an antacid should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Calcium Carbonate; Magnesium Hydroxide: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Because the modified release characteristics are pH-dependent, it is possible that the administration of antacids or other acid suppressants could alter the release of extended-release methylphenidate. Patients receiving an antacid should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate. (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Calcium Carbonate; Risedronate: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Because the modified release characteristics are pH-dependent, it is possible that the administration of antacids or other acid suppressants could alter the release of extended-release methylphenidate. Patients receiving an antacid should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Calcium Carbonate; Simethicone: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Because the modified release characteristics are pH-dependent, it is possible that the administration of antacids or other acid suppressants could alter the release of extended-release methylphenidate. Patients receiving an antacid should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Calcium-channel blockers: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Canagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Canagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Carbamazepine: (Minor) Psychostimulants, such as methylphenidate, 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.
Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Methylphenidate 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.
Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Methylphenidate 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.
Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate 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.
Carbetapentane; Phenylephrine: (Moderate) Methylphenidate 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.
Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Methylphenidate 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.
Carbidopa; Levodopa: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor of dopamine reuptake, and medications that increase dopaminergic activity such as levodopa. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Carbidopa; Levodopa; Entacapone: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor of dopamine reuptake, and COMT inhibitors such as tolcapone and entacapone. Inhibiting the catechol-O-methyltransferase (COMT) enzyme reduces the metabolism of levodopa to metabolites, thereby prolonging the dopaminergic effects of levodopa. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible during concurrent use of methylphenidate and a COMT inhibitor. (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor of dopamine reuptake, and medications that increase dopaminergic activity such as levodopa. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Methylphenidate 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.
Carbinoxamine; Phenylephrine: (Moderate) Methylphenidate 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.
Cardiac glycosides: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics.
Cariprazine: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Carteolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Carvedilol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) Methylphenidate 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; Dextromethorphan; Phenylephrine: (Moderate) Methylphenidate 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; Dihydrocodeine; Phenylephrine: (Moderate) Methylphenidate 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; Phenylephrine: (Moderate) Methylphenidate 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; Phenylephrine: (Moderate) Methylphenidate 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.
Chlorpromazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Chlorthalidone; Clonidine: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and clonidine, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents, including clonidine.
Cimetidine: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of H2-blockers could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
Citalopram: (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 and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Clomipramine: (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Clonidine: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and clonidine, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents, including clonidine.
Clozapine: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Cocaine: (Severe) Additive effects and increased toxicity may be observed when using cocaine in combination with other sympathomimetics. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as CNS stimulation, hypertensive crisis, cardiac arrhythmias or ischemia (angina).
Codeine; Phenylephrine; Promethazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate. (Moderate) Methylphenidate 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) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
Colchicine; Probenecid: (Minor) The response to sympathomimetics may be enhanced by colchicine.
COMT inhibitors: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor of dopamine reuptake, and COMT inhibitors such as tolcapone and entacapone. Inhibiting the catechol-O-methyltransferase (COMT) enzyme reduces the metabolism of levodopa to metabolites, thereby prolonging the dopaminergic effects of levodopa. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible during concurrent use of methylphenidate and a COMT inhibitor.
Dapagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dapagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Desflurane: (Major) Avoid the use of methylphenidate in patients being treated with halogenated anesthestics (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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Desvenlafaxine: (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 and serotonin norepinephrine reuptake inhibitors (SNRIs). Serotonin syndrome has been reported during concurrent use of other serotonergic antidepressants and methylphenidate. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy 45 minutes after ingesting a dose of and SNRI. It is unclear if the reaction was the result of a drug interaction. 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.
Dexlansoprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Dexmethylphenidate: (Severe) Avoid coadministration of methylphenidate and dexmethylphenidate. These drugs represent duplicate treatments. Serious side effects such as nervousness, irritability, arrhythmias, palpitations, seizures, or other stimulant-related adverse effects may occur or get worse during concurrent use.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Methylphenidate 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 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; Promethazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Digitoxin: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics.
Digoxin: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Methylphenidate 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.
Diphenhydramine; Phenylephrine: (Moderate) Methylphenidate 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, an inhibitor 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 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: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Doxazosin: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Doxepin: (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
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 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 and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and serotonin norepinephrine reuptake inhibitors (SNRIs). Serotonin syndrome has been reported during concurrent use of other serotonergic antidepressants and methylphenidate. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy 45 minutes after ingesting a dose of and SNRI. It is unclear if the reaction was the result of a drug interaction. 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.
Dyphylline: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
Dyphylline; Guaifenesin: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
Empagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Empagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Enflurane: (Major) Avoid the use of methylphenidate in patients being treated with halogenated anesthestics (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.
Entacapone: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor of dopamine reuptake, and COMT inhibitors such as tolcapone and entacapone. Inhibiting the catechol-O-methyltransferase (COMT) enzyme reduces the metabolism of levodopa to metabolites, thereby prolonging the dopaminergic effects of levodopa. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible during concurrent use of methylphenidate and a COMT inhibitor.
Ephedrine: (Moderate) Methylphenidate 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: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate 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.
Ertugliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ertugliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Escitalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Esketamine: (Major) Closely monitor blood pressure during concomitant use of esketamine and methylphenidate. Coadministration of psychostimulants, such as methylphenidate, with esketamine may increase blood pressure, including the possibility of hypertensive crisis.
Esmolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Esomeprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Esomeprazole; Naproxen: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Ethanol: (Major) Alcohol consumption should be avoided during treatment with certain extended-release (ER) dosage forms of methylphenidate (e.g., Ritalin LA, Metadate CD). Results from an in vitro study showed that at an alcohol concentration of 40%, there was a 98% release of extended-release methylphenidate (Ritalin LA) from the 40 mg capsule in the first hour after administration. In addition, concurrent use with alcohol may exacerbate the CNS-related adverse effects of methylphenidate.
Ethotoin: (Moderate) Psychostimulants, such as methylphenidate, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as hydantoins. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenytoin or other hydantoins. More frequent monitoring of hydantoin plasma concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on hydantoin 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.
Exenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Famotidine: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of H2-blockers could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
Famotidine; Ibuprofen: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of H2-blockers could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
Fluoxetine: (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 and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Fluoxetine; Olanzapine: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate. (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 and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Fluphenazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Fosphenytoin: (Moderate) Psychostimulants, such as methylphenidate, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as hydantoins. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenytoin or other hydantoins. More frequent monitoring of hydantoin plasma concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on hydantoin 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.
Glimepiride; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Glimepiride; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Green Tea: (Moderate) The CNS stimulant effects of methylphenidate 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 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 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.
Guanabenz: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of guanabenz when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Guanfacine: (Moderate) Psychostimulants, such as methylphenidate, 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 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.
H2-blockers: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of H2-blockers could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
Halogenated Anesthetics: (Major) Avoid the use of methylphenidate in patients being treated with halogenated anesthestics (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.
Haloperidol: (Moderate) Antipsychotics, such as haloperidol, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Halothane: (Major) Avoid the use of methylphenidate in patients being treated with halogenated anesthestics (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.
Hydantoins: (Moderate) Psychostimulants, such as methylphenidate, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as hydantoins. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenytoin or other hydantoins. More frequent monitoring of hydantoin plasma concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on hydantoin 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.
Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Methylphenidate can reduce the hypotensive effect of antihypertensive agents, including methyldopa. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate.
Hydrochlorothiazide, HCTZ; Metoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Hydrochlorothiazide, HCTZ; Spironolactone: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
Hydrochlorothiazide, HCTZ; Triamterene: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
Hydrocodone; Phenylephrine: (Moderate) Methylphenidate 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.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate 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.
Iloperidone: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Incretin Mimetics: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Indapamide: (Moderate) Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as indapamide. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate.
Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Insulins: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Isocarboxazid: (Severe) In general, all types of sympathomimetics and psychostimulants should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and even respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Isoflurane: (Major) Avoid the use of methylphenidate in patients being treated with halogenated anesthestics (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.
Labetalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Lansoprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Lansoprazole; Naproxen: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Levobetaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Levobunolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Levodopa: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor of dopamine reuptake, and medications that increase dopaminergic activity such as levodopa. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Levomilnacipran: (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 and serotonin norepinephrine reuptake inhibitors (SNRIs). Serotonin syndrome has been reported during concurrent use of other serotonergic antidepressants and methylphenidate. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy 45 minutes after ingesting a dose of and SNRI. It is unclear if the reaction was the result of a drug interaction. 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.
Levothyroxine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
Levothyroxine; Liothyronine (Porcine): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
Linezolid: (Major) Psychostimulants, such as methylphenidate, 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) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Lithium: (Moderate) Methylphenidate can occasionally worsen mania in those with bipolar disorder, potentially reducing the overall effectiveness of treatment with mood stabilizers. According to some literature and the product labeling of many stimulants, lithium may antagonize the anorectic and stimulant effects of amphetamines. Despite this precaution, some data indicate a beneficial effect based upon the clinical circumstances of the patient. Further study is needed to fully assess the benefits and risks that may occur from concomitant administration of methylphenidate and lithium. Close monitoring is advisable when combination therapy is initiated or dosages are increased.
Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Loop diuretics: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as loop diuretics.
Loxapine: (Moderate) Antipsychotics, such as loxapine, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Lurasidone: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Magnesium Hydroxide: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
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.
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; Promethazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Mephobarbital: (Moderate) Psychostimulants, such as methylphenidate, may lower the seizure threshold, thereby reducing the efficacy of barbiturates such as mephobarbital in treating seizures. In addition, case reports suggest a potential pharmacokinetic interaction between methylphenidate and barbiturates such as phenobarbital; however, a kinetic interaction was not confirmed when evaluated at higher sample sizes. Nevertheless, a dose adjustment of the barbiturate may be required when initiating or discontinuing methylphenidate. It should be noted that methylphenidate is not metabolized by the cytochrome P450 system to a relevant extent and methylphenidate has no relevant inhibitory effect on CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A.
Mesoridazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Metformin; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Metformin; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate 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: (Minor) Methylphenidate can reduce the hypotensive effect of antihypertensive agents, including methyldopa. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate.
Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and methylphenidate 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 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 blocks central dopamine reuptake, which increases central dopaminergic functioning, while metoclopramide is a dopamine antagonist.
Metoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Midodrine: (Moderate) Methylphenidate 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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and serotonin norepinephrine reuptake inhibitors (SNRIs). Serotonin syndrome has been reported during concurrent use of other serotonergic antidepressants and methylphenidate. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy 45 minutes after ingesting a dose of and SNRI. It is unclear if the reaction was the result of a drug interaction. 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.
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 and mirtazapine. 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.
Modafinil: (Major) The use of modafinil with other psychostimulants, including methylphenidate, 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.
Molindone: (Moderate) Antipsychotics, such as molindone, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Monoamine oxidase inhibitors: (Severe) In general, all types of sympathomimetics and psychostimulants should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and even respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
Nadolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Nebivolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Nebivolol; Valsartan: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Nefazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate 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.
Nitrates: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Nizatidine: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of H2-blockers could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
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 should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Norepinephrine: (Moderate) Methylphenidate 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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Olanzapine: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Omeprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Omeprazole; Sodium Bicarbonate: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate. (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Paliperidone: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Pantoprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Paroxetine: (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 and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Penbutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Pergolide: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor 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.
Perphenazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Perphenazine; Amitriptyline: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate. (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Phenelzine: (Severe) In general, all types of sympathomimetics and psychostimulants should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and even respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Phenobarbital: (Moderate) Psychostimulants, such as methylphenidate, 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.
Phenothiazines: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Phenoxybenzamine: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Phentolamine: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Phenylephrine: (Moderate) Methylphenidate 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.
Phenylephrine; Promethazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate. (Moderate) Methylphenidate 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.
Phenytoin: (Moderate) Psychostimulants, such as methylphenidate, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as hydantoins. Some human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of phenytoin or other hydantoins. More frequent monitoring of hydantoin plasma concentrations may be required when initiating or discontinuing methylphenidate. The mechanism of the potential effect on hydantoin 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.
Pimozide: (Major) Pimozide should not be used in patients taking drugs 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. Pimozide and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Pindolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Potassium-sparing diuretics: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
Pramipexole: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor 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: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Primidone: (Moderate) Psychostimulants, such as methylphenidate, 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.
Prochlorperazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Promethazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Propranolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Proton pump inhibitors: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Protriptyline: (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Quetiapine: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Rabeprazole: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
Ranitidine: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of H2-blockers could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.
Reserpine: (Major) Coadministration of methylphenidate and reserpine should be avoided if possible. Methylphenidate and reserpine may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on neurotransmitters. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space while reserpine depletes stores of serotonin and norepinephrine in the brain, adrenal medulla, and other tissues, and reduces the reuptake of catecholamines by adrenergic nerve terminals. Reserpine binds tightly to catecholamine storage vesicles in the adrenergic neuron, eventually destroying these vesicles so that the terminals cannot concentrate or store norepinephrine or dopamine. This process also occurs in vesicles that store serotonin.
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) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Ropinirole: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor 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 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.
Safinamide: (Severe) Safinamide is contraindicated for use with methylphenidate due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Safinamide is a selective inhibitor of monoamine oxidase B, the enzyme which metabolizes dopamine. At high doses, diminished metabolism of serotonin and norepinephrine are also possible through inhibition of MAO-A. There is some evidence that the alteration of dopamine transport systems by methylphenidate may indirectly augment the action of serotonin.
Selective serotonin reuptake inhibitors: (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 and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Selegiline: (Severe) In general, all types of sympathomimetics and psychostimulants should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and even respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Selexipag: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Semaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Serotonin norepinephrine reuptake inhibitors: (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 and serotonin norepinephrine reuptake inhibitors (SNRIs). Serotonin syndrome has been reported during concurrent use of other serotonergic antidepressants and methylphenidate. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy 45 minutes after ingesting a dose of and SNRI. It is unclear if the reaction was the result of a drug interaction. 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.
Sertraline: (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 and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
Sevoflurane: (Major) Avoid the use of methylphenidate in patients being treated with halogenated anesthestics (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 and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sibutramine: (Major) The use of methylphenidate with sibutramine should be approached with great caution, due to the risk for serotonin syndrome. Blood pressure and heart rate will require periodic monitoring, since additive effects may occur. Sibutramine has not been studied in combination with stimulants that are not used for weight loss, such as methylphenidate. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. Sibutramine may cause serotonin syndrome, and serotonin syndrome has been rarely reported with methylphenidate-type agents. Serotonin syndrome risk increases when 2 or more drugs with this effect are used together. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
Sodium Bicarbonate: (Minor) The modified release characteristics of extended-release methylphenidate (Ritalin LA) are pH-dependent. Administration of antacids could alter the release of methylphenidate. Patients receiving extended-release methylphenidate with antacids should be monitored for adverse effects and/or reduced efficacy.
Sodium Oxybate: (Moderate) The stimulant effects of methylphenidate 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, a CNS stimulant. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
Sotalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Spironolactone: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
St. John's Wort, Hypericum perforatum: (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 and St. John's Wort. There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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.
Sulfonylureas: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Tedizolid: (Moderate) Psychostimulants, such as methylphenidate, 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
Terazosin: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia.
Thiazide diuretics: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as thiazide diuretics.
Thiazolidinediones: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Thiethylperazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Thioridazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Thiothixene: (Moderate) Antipsychotics, such as thiothixene, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Thyroid hormones: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation.
Tolcapone: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor of dopamine reuptake, and COMT inhibitors such as tolcapone and entacapone. Inhibiting the catechol-O-methyltransferase (COMT) enzyme reduces the metabolism of levodopa to metabolites, thereby prolonging the dopaminergic effects of levodopa. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible during concurrent use of methylphenidate and a COMT inhibitor.
Tranylcypromine: (Severe) In general, all types of sympathomimetics and psychostimulants should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and even respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Triamterene: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
Tricyclic antidepressants: (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
Trifluoperazine: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
Trimipramine: (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 and tricyclic antidepressants (TCAs). There are rare reports of serotonin syndrome occurring during use of other serotonergic antidepressants (i.e., SSRIs) and methylphenidate. 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. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of TCAs. A dose adjustment of the TCA, and monitoring of TCA plasma concentrations when applicable, may be required when initiating or discontinuing methylphenidate.
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.
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.
Vasopressors: (Moderate) Methylphenidate 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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and serotonin norepinephrine reuptake inhibitors (SNRIs). Serotonin syndrome has been reported during concurrent use of other serotonergic antidepressants and methylphenidate. There is also a case of a neuroleptic malignant syndrome-like reaction occurring in a child on chronic methylphenidate therapy 45 minutes after ingesting a dose of and SNRI. It is unclear if the reaction was the result of a drug interaction. 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.
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 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 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 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. Case reports suggest a potential interaction between methylphenidate and coumarin anticoagulants. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of warfarin. The mechanism of the potential interaction is not clear. Methylphenidate is not metabolized by the CYP450 system to a relevant extent and methylphenidate has no relevant inhibitory effect on CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A. ; however, pharmacokinetic interactions were not confirmed when explored at higher sample sizes. Nevertheless, a dose adjustment of warfarin and more frequent monitoring of the INR may be required when initiating or discontinuing methylphenidate.
Ziprasidone: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.