# Relexxii ### (methylphenidate hydrochloride extended-release, OROS) **[Relexxii](https://wiki.joshnp.com/books/drug-library/page/relexxii)** (methylphenidate hydrochloride extended-release, OROS); CII
[**Full Prescribing Information**](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=22d5fa47-b5b9-4fd9-980c-4eb88e95ae5d&type=display)[**DailyMed Drug Information**](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=22d5fa47-b5b9-4fd9-980c-4eb88e95ae5d)
--- ### **Summary** Relexxii is a long-acting methylphenidate tablet using the same class of OROS osmotic delivery as Concerta, approved for ADHD from age 6 through 65. Its differentiator is the strength ladder: 45 mg, 63 mg and 72 mg exist as single tablets, so a patient needing more than 54 mg takes one tablet rather than two. It is not labeled as bioequivalent to Concerta. Schedule II; brand and authorized generic. --- ### **Forms & Strengths** - Extended-release tablets (OROS, swallow whole): 18 mg, 27 mg, 36 mg, 45 mg, 54 mg, 63 mg, 72 mg --- ### **Dosing** - **Age:** 6 to 65 y/o - **Onset:** ~ 1 hour - **Duration:** up to 12 hours - **Release Profile:** 18% IR / 82% ER via OROS osmotic delivery - **Initial Dose:** - 6 to 17 y/o, new to methylphenidate: 18 mg once daily in the morning - 18 to 65 y/o, new to methylphenidate: 18 mg or 36 mg once daily in the morning - From methylphenidate 2-3 times daily, per dose: 5 mg to 18 mg; 10 mg to 36 mg; 15 mg to 54 mg; 20 mg to 72 mg - **Titration:** 18 mg every 7 days; 27, 45 and 63 mg give intermediate steps - **Max Dose:** - 6 to 12 y/o: 54 mg/day - 13 to 17 y/o: 72 mg/day, not to exceed 2 mg/kg/day - 18 to 65 y/o: 72 mg/day - **Considerations:** Swallow whole; chewing or dividing destroys the osmotic pump. The 45, 63 and 72 mg strengths avoid two-tablet regimens above 54 mg. Do not substitute milligram-for-milligram with another methylphenidate. --- ### **Pharmacology** - **Mechanism:** Blocks presynaptic dopamine and norepinephrine reuptake at DAT and NET; does not meaningfully promote catecholamine release at therapeutic doses - **Delivery / Release:** 18% IR / 82% ER via OROS osmotic delivery. The overcoat dissolves within an hour, then a push layer forces drug through a laser-drilled orifice; two core layers make release rise over 6 to 7 hours. - **Metabolism:** De-esterified to PPAA (ritalinic acid), inactive. Half-life ~3.5 hours, ~90% recovered in urine. Renal impairment has little effect. - **Class Positioning:** Same osmotic principle as [Concerta](https://wiki.joshnp.com/link/11), not the same product: 18% against 22% immediate fraction, Tmax 5.5 h against 6 to 10 h, no bioequivalence study. Advantage: single-tablet dosing at 45, 63 and 72 mg. --- ### **Indications** - **ADHD** (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6 to 65 y/o --- ### **Off-Label Uses** - **ADHD in children 4 to 5 years old** (ICD-10: F90.x): behavioral parent training first line; if medication is needed use IR methylphenidate, not OROS. Expert consensus. (AAP 2019) - **Narcolepsy** (ICD-10: G47.419): IR methylphenidate carries this indication, Relexxii does not. Insufficient. - **Substituting for Concerta at the same strength:** common at 18 to 54 mg but unsupported by any bioequivalence study. Recheck response after a switch. Insufficient. - **Where the evidence does not support use:** treatment-resistant depression, binge eating disorder, cancer-related and chronic fatigue. Adult literature only; insufficient in children. (AHRQ 2024) - **Cognitive enhancement in a youth without ADHD:** not an indication and not supported. --- ### **Contraindications & Warnings** - **Boxed Warning:** Abuse, misuse and addiction, with overdose and death. Assess abuse risk before prescribing and reassess throughout treatment. - **Contraindicated:** - Hypersensitivity to methylphenidate; angioedema and anaphylaxis reported - MAOI use, current or within 14 days: hypertensive crisis - **Use with caution:** - Structural cardiac abnormality, cardiomyopathy, arrhythmia or coronary disease: avoid - Pre-existing hypertension: monitor blood pressure and pulse - Psychotic or bipolar disorder: exacerbation and treatment-emergent mania - GI narrowing: the tablet is nondeformable - Significant hyperopia or angle-closure risk: refer to ophthalmology - Personal or family history of tics or Tourette's syndrome - Substance use disorder in the patient or the household - **Screen before starting:** - Cardiac history and exam including family sudden death; the label requires no routine ECG - Tics, and risk factors for a manic episode - Abuse and diversion risk in patient and household - Ability to swallow a tablet whole; any GI stricture or bowel surgery - Baseline height, weight, blood pressure and heart rate --- ### **Drug Interactions** - **MAOIs** (phenelzine, tranylcypromine, selegiline, linezolid, methylene blue): hypertensive crisis. Contraindicated within 14 days. - **Antihypertensives:** effectiveness reduced. Increase BP monitoring and adjust the antihypertensive. - **Halogenated anesthetics** (sevoflurane, isoflurane, desflurane): intraoperative BP and HR surge. Hold on the day of surgery. - **Risperidone:** EPS may increase when either dose changes in either direction. Monitor across any titration. - **Serotonergic agents** (SSRIs, SNRIs, TCAs, triptans, tramadol): serotonin syndrome in postmarketing reports only, not in the interaction table. Counsel on symptoms. --- ### **Administration** - Once daily in the morning, with or without food. - Swallow whole. Do not chew, divide or crush; there is no sprinkle option. - If the child cannot swallow a tablet, use a bead capsule ([Ritalin LA](https://wiki.joshnp.com/link/30)) or a liquid ([Quillivant XR](https://wiki.joshnp.com/link/28)). - The intact shell passes in the stool; warn the family before the first dose. - Never substitute milligram-for-milligram; use the labeled conversion table and recheck response after any switch. - Missed dose: skip it rather than giving it late in the day. - Store locked; the 63 and 72 mg strengths are high-value diversion targets. --- ### **Side Effects** - **Common, pediatric 6 to 17 y:** upper abdominal pain, the only reaction above 5%; insomnia, nasopharyngitis, vomiting, pyrexia 2% to 3%. - **Common, adults** (all above 5%): decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight loss, irritability, hyperhidrosis. - **Serious:** - Sudden death with structural cardiac disease: avoid the drug in that population - New psychosis or mania, including with no psychiatric history: consider discontinuing - Priapism, sometimes surgical, typically after a dose increase and also during drug holidays - Peripheral vasculopathy and Raynaud's with digital ulceration: assess digits each visit - Long-term growth suppression; GI obstruction from the nondeformable tablet in pre-existing narrowing - Acute angle closure glaucoma; new or worsening tics and Tourette's - Postmarketing: convulsion, dyskinesia, serotonin syndrome, hypersensitivity reactions --- ### **Monitoring & Labs** - **Cardiovascular:** BP and HR at baseline, at every dose change, and at least every 6 months. - **Growth:** height, weight and BMI at baseline and every 6 months; failure to gain triggers interruption. - **Appetite and sleep:** at every visit and dose change; the usual reasons titration stalls short of 72 mg. - **Psychiatric and tics:** screen for psychosis, mania, aggression, depressed mood and tics at baseline and every visit. - **Abuse and diversion:** at every refill, pill count, ask about sharing and selling, check the PDMP. A boxed-warning obligation. - **Dose ceiling:** at every titration step in a 13 to 17 year old, recalculate 2 mg/kg/day. Under 36 kg the weight cap bites before the 72 mg cap. - **Laboratory:** none is required by this label. --- ### **Discontinuation & Taper** - No taper required; the label gives no tapering schedule. - Discontinue if no improvement after appropriate dose adjustment over one month. - Withdrawal after prolonged use: dysphoria, fatigue, vivid dreams, sleep change, increased appetite. - Priapism has occurred during drug holidays and on discontinuation. - Drug holidays are reasonable where growth or appetite limits treatment; an interrupted day is fully unmedicated. --- ### **Pregnancy & Lactation** - **Pregnancy:** no drug-associated risk of major birth defects or miscarriage identified. Stimulant vasoconstriction may reduce placental perfusion. Background risk 2% to 4% and 15% to 20%. Weigh against untreated maternal ADHD. - **Lactation:** infant dose 0.16% to 0.7% of the maternal weight-adjusted dose; undetectable in infant serum in every reported case, including 72 mg daily. Not a reason to stop breastfeeding. (LactMed 2025) - **Lactation, milk supply:** prolactin falls; large doses may interfere before supply is established. Monitor the infant for agitation, anorexia and poor weight gain. (LactMed 2025) - **Exposure Registry:** National Pregnancy Registry for ADHD Medications, 1-866-961-2388. --- ### **Counseling Points** - **Counsel the family on:** - Relexxii and Concerta not being the same tablet even where milligrams match; watch the first week after a substitution. - The 45, 63 and 72 mg strengths being the reason for this product: one tablet replaces two. - Seeing the intact shell in the stool; it is the spent pump, not a wasted dose. - Half a 45 mg tablet being a broken osmotic pump, not 22.5 mg. - Dosing at the same early hour daily; a late dose pushes the ascending peak into the evening. - Moving the largest meal to breakfast and the evening, when appetite returns. - Locked storage; the high strengths are the ones peers ask for. - **Advise them to call for:** - Chest pain, fainting, or a racing heart that does not settle. - New hallucinations, or new suspicious or fearful thinking. - Numbness, coldness or colour change in fingers or toes. - A new or markedly worse tic. - A painful erection lasting more than a few hours; a surgical emergency. - Severe abdominal pain or vomiting, especially with any history of bowel narrowing. - Eye pain with blurred vision or halos around lights. - Clothes fitting more loosely, or no weight gain across a few months. --- ### **References** 1. DailyMed. Relexxii (methylphenidate hydrochloride) extended-release tablets prescribing information. Vertical Pharmaceuticals. 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=22d5fa47-b5b9-4fd9-980c-4eb88e95ae5d 2. DailyMed. Concerta (methylphenidate hydrochloride) extended-release tablets prescribing information. Janssen Pharmaceuticals. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a88218c-5b18-4220-8f56-526de1a276cd 3. FDA. openFDA National Drug Code Directory, generic\_name methylphenidate. 2026. https://api.fda.gov/drug/ndc.json?search=generic\_name:%22methylphenidate%22&limit=1000 4. LactMed. Methylphenidate. Drugs and Lactation Database, NICHD. 2025. https://www.ncbi.nlm.nih.gov/books/NBK501310/ 5. American Academy of Pediatrics. Clinical practice guideline for the diagnosis, evaluation, and treatment of ADHD in children and adolescents. Pediatrics. 2019. https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/ 6. AHRQ. Attention deficit hyperactivity disorder: diagnosis and treatment in children and adolescents. Comparative Effectiveness Review No. 267. 2024. https://www.ncbi.nlm.nih.gov/books/NBK602989/