appreciably change in shape in the GI tract Do not administer to patients with pre-existing severe gastrointestinal narrowing conditions, including esophageal motility disorders,small bowel inflammatory disease, "short gut" syndrome due to adhesions or decreased transit time, cystic fibrosis, history of peritonitis, or chronic intestinal pseudo-obstruction, or Meckel diverticulum Use only in patients who can swallow tablets whole Psychiatric adverse reactions CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder CNS stimulants may also induce a manic or mixed episode in patients Before initiating treatment, screen for risk factors for developing a manic episode (eg, history or family history of suicide, bipolar disorder, and depression) CNS stimulants at recommended doses, may cause psychotic or manic symptoms (eg, hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania; consider discontinuing therapy if such symptom occur Serious cardiovascular reactions Sudden death, stroke, and myocardial infarction report in adults Sudden death reported in pediatric patients with structural cardiac abnormalities and other serious heart problems Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, and other serious heart problems Further evaluate for developing exertional chest pain, unexplained syncope, or arrhythmias during treatment Adhansia XR only 45-mg capsules contain FD&C yellow #5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons Drug interaction overview MAOIs Contraindicated Do administer during or within 14 days of discontinuing MAOI treatment Coadministration of MAOIs with CNS stimulants can cause hypertensive crisis, which increases the risk of death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure Antihypertensive drugs Monitor BP and adjust dose of antihypertensive drugs accordingly Methylphenidate may decrease effectiveness of antihypertensive drugs Halogenated anesthetics Avoid using methylphenidate on day of surgery Methylphenidate concomitantly used halogenated anesthetics may potentiate the risk of sudden BP and HR increase during surgery Risperidone Monitor for signs of extrapyramidal symptoms (EPS) Dose changes in either risperidone and/or methylphenidate may increase the risk of EPS Gastric pH modulators (Adhansia XR, Cotempla XR-ODT only) Monitor and use alternant based on clinical response Gastric pH modulators (eg, proton pump inhibitors, H2-blockers) may change the release, pharmacokinetic profiles, and pharmacodynamics of Adhansia XR Pregnancy Published studies and postmarketing reports on use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes Animal data No teratogenic effects were observed with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses up to 2x and 9x the maximum recommended human dose (MRHD) of 100 mg/day given to adolescents on a mg/m2 basis, respectively However, spina bifida was observed in rabbits at a dose 31x the MRHD given to adolescents Decrease in pup body weight was observed in a pre- and postnatal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 3.5x the MRHD given to adolescents Clinical considerations CNS stimulant medications can cause vasoconstriction and thereby decrease placental perfusion No fetal and/or neonatal adverse reactions reported with use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers Pregnancy exposure registry Monitors pregnancy outcomes in females exposed to ADHD medications Encourage providers to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 Lactation Limited published literature, based on breast milk sampling from five mothers, reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7 There are no reports of adverse effects on breastfed infant and no effects on milk production; however, long-term neurodevelopmental effects on infants from CNS stimulant exposure are unknown Monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gainPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Unknown; may block reuptake of norepinephrine and dopamine into presynaptic neurons; may stimulate CNS similar to amphetamines; may stimulate cerebral cortex and subcortical structures Absorption Bioavailability Aptensio XR: 101-102% Jornay PM: 73.9% Peak plasma concentration ER tablets: 19.3-19.7 ng/mL(72-mg dose); 3.7 ng/mL (18 mg-dose) Aptensio XR: 23.47 ng/mL (capsule); 21.78 ng/mL (sprinkle) Peak plasma time ER tablets: 5.5 hr (72-mg dose); 6.8 hr (18-mg dose) Adhansia XR: 1.5 hr (1st median range time); 12 hr (2nd median range time) Aptensio XR: 2 hr Jornay PM: 14 hr AUC ER tablets: 200.9-206.1 ng⋅hr/mL (72-mg dose); 41.8 ng⋅hr/mL (18-mg dose) Aptensio XR: 258.1-262.7 ng⋅hr/mL (capsule): 258-262.9 ng⋅hr/mL (sprinkle) Distribution Plasma methylphenidate concentrations in adults and pediatric patients 13-17 years decline biexponentially following oral administration Vd: 2.65 L/kg (d-methylphenidate); 1.8 L/kg ( l-methylphenidate) Metabolism Primarily metabolized by de-esterification to PPAA (little or no pharmacologic activity) Elimination Half-life ER tablets: 3.5 hr (18-mg dose) Aptensio XR: 5.09 hr (capsule); 5.43 hr (sprinkle) Jornay PM: 5.9 hr Metadate CD: 6.8 hr Immediate-release tablets: 2.9 hr Excretion Urine: 90% (80% main urinary metabolite PPAA) Oral Administration Do not substitute for other methylphenidate products on an mg-per-mg basis, because of different methylphenidate base compositions and differing pharmacokinetic profiles Concerta or Relexxii Take orally in the morning with or without food Swallow tablet whole with liquid; do not chew, divide, or crush QuilliChew ER Extended-release chewable tablet Take once in morning May take with or without food Switching from other methylphenidate products If switching from other methylphenidate products, discontinue that treatment, and titrate with QuilliChew ER using the titration schedule (see Pediatric Dosing) Methylin ER tablet Swallow whole; do not crush or chew Take 30-45 minutes before meals Ritalin Ritalin: Swallow whole, do not crush or chew Ritalin LA capsule: Swallow whole, do not crush or chew; may open capsule and sprinkle contents on applesauce and consumed immediately Take all formulations 30-45 minutes before meals Metadate Metadate CD: Swallow whole, do not crush or chew; may open capsule and sprinkle contents on applesauce and consumed immediately; administer once daily in AM Quillivant XR Oral extended-release suspension Shake bottle vigorously for at least 10 seconds before measuring dose May take with or without food Aptensio XR May take with or without food Advise patients to establish a routine pattern regarding meals Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce and consume immediately Cotempla XR-ODT Take consistently with or without food Use dry hands when opening the blister pack Do not remove the tablet from the blister pack until just before dosing Remove tablet by peeling back foil on blister pack; do not push the tablet through the foil Do not store tablet for future use Administer immediately after opening by placing the tablet on patient’s tongue and letting it dissolve; do not chew or crush Disintegrate in saliva so that it can be swallowed; no liquid is needed to take the tablet Jornay PM Not to be administered in the morning Following determination of optimal administration time, advise patients to maintain a consistent dosing time Advise patients to take the dose consistently either with or without food May take capsule whole, or may be opened and the entire contents sprinkled onto applesauce; if patient is using the sprinkled administration method, the sprinkled applesauce should be consumed immediately and not stored and should be taken in its entirety without chewing; the dose of a single capsule should not be divided and should be taken at the same time Periodically reevaluate long term use and adjust dosage as needed Missed dose Take dose as soon possible that same evening; if patient remembers the missed dose the following morning, skip missed dose and wait until next scheduled evening administration Switching from other methylphenidate products If switching from other methylphenidate products, discontinue that treatment, and titrate with Jornay PM using the titration schedule described above Adhansia XR Swallow whole or open capsule and sprinkle entire contents onto 1 tablespoon of applesauce or yogurt; consume entire mixture immediately or within 10 min Take the entire contents of capsule sprinkled on chosen food in its entirety, without chewing Discard mixture if not consumed within 10 min; do not store Do not divide capsules nor take <1 capsule/day Missed dose Do not administer later in the day Do not administer additional medication to make up for missed Switching from other methylphenidate products Switching from other methylphenidate products: Discontinue current treatment and titrate with Adhansia XR using titration schedule Storage Metadate CD: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F); protect from light and moisture Concerta. Relexxii: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F); protect from humidity Adhansia XR: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F); protect from light Extended-release chewable (QuilliChew ER): Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) Extended-release orally disintegrating (Cotempla XR-ODT): Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F); store in reusable travel case Immediate-release (Ritalin): Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F); protect from light BRAND FORM. UNIT PRICE PILL IMAGE methylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 27 mg tabletmethylphenidate HCl oral- 10 mg chewable tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 27 mg tabletmethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 2.5 mg chewable tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 36 mg tabletmethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 5 mg chewable tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 36 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 36 mg tabletmethylphenidate HCl oral- 27 mg tabletmethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 27 mg tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 36 mg tabletmethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 30 mg capsulemethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 40 mg capsulemethylphenidate HCl oral- 50 mg capsulemethylphenidate HCl oral- 60 mg capsulemethylphenidate HCl oral- 50 mg capsulemethylphenidate HCl oral- 27 mg tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 50 mg capsulemethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 40 mg capsulemethylphenidate HCl oral- 20 mg capsulemethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 15 mg capsulemethylphenidate HCl oral- 10 mg capsulemethylphenidate HCl oral- 5 mg chewable tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 2.5 mg chewable tabletmethylphenidate HCl oral- 27 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 36 mg tabletmethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 36 mg tabletmethylphenidate HCl oral- 27 mg tabletmethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 5 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 5 mg/5 mL solutionmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 40 mg capsulemethylphenidate HCl oral- 10 mg capsulemethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 10 mg tabletmethylphenidate HCl oral- 30 mg capsulemethylphenidate HCl oral- 20 mg capsulemethylphenidate HCl oral- 36 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 54 mg tabletmethylphenidate HCl oral- 20 mg tabletmethylphenidate HCl oral- 30 mg capsulemethylphenidate HCl oral- 40 mg capsulemethylphenidate HCl oral- 20 mg capsulemethylphenidate HCl oral- 18 mg tabletmethylphenidate HCl oral- 30 mg capsulemethylphenidate HCl oral- 20 mg capsulemethylphenidate HCl oral- 10 mg capsulemethylphenidate HCl oral- 50