Relexxii

(methylphenidate hydrochloride extended-release, OROS)

Relexxii (methylphenidate hydrochloride extended-release, OROS); CII

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, 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) or a liquid (Quillivant XR).
• 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/