Ritalin (Methylphenidate) is a brain stimulant that is used in the treatment of patients with Narcolepsy (excessive daytime sleepiness and sudden attacks of sleepiness) and attention deficit hyperactivity disorder (ADHD).

Methylphenidate (Ritalin) Uses:

• Attention-deficit/hyperactivity disorder:

  • For the treatment of attention-deficit/hyperactivity disorder (ADHD)

• Narcolepsy (Methylin, Metadate ER, Ritalin, and Ritalin SR):

  • Management of narcolepsy (Symptomatic)

• Off Label Use Of Methylphenidate in Adults:

  • Depression (terminal illness, palliative care, medically ill);
  • Fatigue, cancer related;
  • Major depressive disorder (antidepressant augmentation; geriatric patients)

Read: Dextroamphetamine (Dexedrine); Dose, Side effects, Warnings

Methylphenidate (Ritalin) Dose in Adults

Methylphenidate (Ritalin) Use in the treatment of ADHD:

• Immediate-release (IR) products (tablets, chewable tablets, and solution):

  • Initial: 5 mg orally two times a day, before breakfast and lunch; dose should be increased by 5 to 10 mg daily at weekly intervals; maximum dose: 60 mg per 24 hours (in 2 to 3 divided doses).

• Extended-release (ER), sustained-release (SR) products (capsules, tablets, chewable tablets, orally disintegrating tablets, and oral suspension):

  • Concerta: (Adults <65 years):

    • Patients not currently taking methylphenidate:

      • Initial: 18 to 36 mg orally once daily in the morning

    • Patients currently taking immediate release (IR) methylphenidate or sustained release (SR) [Canadian product]:

      • Initial: Note: Dosing based on current regimen and clinical judgment; suggested dosing listed below:

      • IR methylphenidate: -

        • Patients taking IR methylphenidate 5 mg 2 to 3 times daily: 18 mg orally once daily in the morning
        • Patients taking IR methylphenidate 10 mg 2 to 3 times daily: 36 mg orally once daily in the morning
        • Patients taking IR methylphenidate 15 mg 2 to 3 times daily: 54 mg orally once daily in the morning
        • Patients taking IR methylphenidate 20 mg 2 to 3 times daily: 72 mg orally once daily in the morning
      • SR methylphenidate (Concerta Canadian product labeling 2017):
        • Patients taking methylphenidate SR 20 mg daily: 18 mg orally once daily in the morning
        • Patients taking methylphenidate SR 40 mg daily: 36 mg orally once daily in the morning
        • Patients taking methylphenidate SR 60 mg daily: 54 mg orally once daily in the morning
      • Dose adjustment:
        • • The dose may be increased in increments of 18 mg at weekly intervals.
          • 27 mg dosage strength of is available for situations in which a dosage between 18 to 36 mg is desired.
          • Maximum dose: 72 mg per 24 hours.

  • Aptensio XR:

    • Initial: 10 mg orally in OD dose; may titrate in 10 mg increments at weekly intervals; maximum: 60 mg per 24 hours.

  • Biphentin [Canadian product]:

    • Patients not currently taking methylphenidate:

      • Initial: 10 to 20 mg orally in OD dose; may adjust in 10 mg increments at weekly intervals to a maximum dose of 80 mg per 24 hours.

    • Conversion from immediate-release methylphenidate formulations to Biphentin:

      • The equivalent total daily dose should be used & given  in OD dose.

  • Foquest [Canadian product]:

    • Patients not currently taking methylphenidate:

      • Initial: 25 mg orally in OD dose; the dose should be adjusted at 5 day intervals as needed to the lowest effective dose (maximum: 100 mg per 24 hours).

    • Patients currently taking methylphenidate:

      • Initiate Foquest with the next lower strength based on total methylphenidate daily dose; the dose should be adjusted at 5 day intervals as needed to the lowest effective dose (maximum: 100 mg per 24 hours).

Note: Do not substitute immediate release formulations or other controlled release formulations with Foquest on a milligram for milligram basis (pharmacokinetic profiles differ).

• Jornay PM:

  • Initial: 20 mg orally in OD dose in the evening between 6:30 and 9:30 PM (eg, 8:00 PM); dose may be increased in increments of 20 mg per 24 hours at weekly intervals to a maximum daily dose of 100 mg per 24 hours.

Note: If converting from another methylphenidate formulation, discontinue previous formulation and titrate Jornay PM using this same schedule; do not substitute on a milligram-per-milligram basis.

• Metadate ER, Ritalin-SR:

  • Give twice or thrice daily; the immediate-release tablets should be replaced when the divided dosage corresponds to sustained-/extended-release tablet strength (duration of action: ~8 hours); maximum: 60 mg per 24 hours.

• Metadate CD, Quillivant XR:

  • Initial: 20 mg orally in OD dose; may adjust in 10 to 20 mg increments at weekly intervals; maximum: 60 mg per 24 hours.

  • Conversion from other methylphenidate formulations to Quillivant XR:

    • Discontinue previous formulation and titrate using above schedule; do not substitute on a milligram-per-milligram basis

• QuilliChew E R:

  • Initial: 20 mg orally in OD dose in the morning; dose may be adjusted by 10, 15 or 20 mg at weekly intervals (tablets are scored and may be broken in half to achieve the 10 mg and 15 mg doses); maximum: 60 mg per 24 hours.

  • Conversion from other methylphenidate formulations to QuilliChew ER:

    • Discontinue previous formulation and titrate using above schedule; do not substitute on a milligram-per-milligram basis

• Ritalin LA:

  • Initial: 20 mg orally in OD dose( may consider 10 mg once a day for some patients); may adjust in 10 mg increments at weekly intervals; maximum: 60 per 24 hours.

  • Conversion from immediate-release or sustained-release methylphenidate formulation to Ritalin LA:

    • Equivalent total daily dose should be given in OD dose.

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Methylphenidate (Ritalin) Use in the Narcolepsy:

• Immediate-release tablets and solution (Methylin, Ritalin):

  • Initial: 5 mg orally two times a day before breakfast and lunch; dose should be increased by 5 to 10 mg everyday at weekly intervals to a maximum dose of 60 per 24 hours(in 2 to 3 divided doses).

• Extended- and sustained-release tablets (Metadate ER, Ritalin-SR):

  • Give twice or thrice daily (orally).
  • The immediate-release tablets should be replaced when the divided dosage corresponds to sustained-/extended-release tablet strength (duration of action: ~8 hours); maximum: 60 mg per 24 hours.

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Methylphenidate (Ritalin) use in the treatment of depression in patients with a terminal illness (for palliative care in the medically ill patient):

• Immediate release:

  • 5 to 5 mg orally once a day before breakfast or twice a day before breakfast and lunch; dose should be increased by 2.5 to 5 mg daily every 1 to 3 days in divided doses before breakfast and lunch as tolerated to a maximum dose of 20 to 40 mg per 24 hours.
  • Sustained release should not be used

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Methylphenidate (Ritalin) use in the treatment of cancer-related Fatigue:

• Immediate release:

  • Initial: 5 mg orally two times a day (at 8 am and 1 pm); dose should be increased based on tolerability in increments of 10 mg per 24 hours every 3 days up to a maximum of 40 mg per 24 hours.

Methylphenidate (Ritalin) Dose in Children

Methylphenidate (Ritalin) Use in the treatment of Attention deficit-hyperactivity disorder (ADHD):

Both for children and adolescents methylphenidate is recommended as 1st-line therapy ; it is also recommended to give a discontinuation trial after 6 months of therapy to reassess underlying psychopathology.

Note: The medication should be discontinued if no improvement is seen after appropriate dosage adjustment over a 1-month period of time . Oral:

• Immediate-release products (eg, Methylin, Ritalin):

  • Children 3 to 5 years, moderate to severe dysfunction:
    • Limited data is available. AAP considers this patient population 1st-line agent if necessary. The American Academy of Child and Adolescent Psychiatry Preschool Psychopharmacology Working Group recommended discontinuation of treatment after six months of treatment in preschoolers in order to reassess the underlying psychopathology.
    • A variable response may occur and it may not be as robust as that seen in older pediatric patients. Of note, the number or severity of comorbidities can predict treatment response to methylphenidate. For example, a small treatment response was predicted by no more than one comorbidity, whereas a larger response was predicted for children who are school-aged. However, if there were three or more comorbidities, this could have an effect on treatment response.
    • Initial: 2.5 mg p/o two times a day, the dose may be titrated gradually to 7.5 mg twice or thrice daily over 2 to 4 weeks; others may use a rapid titration to 7.5 mg 3 times daily within 1 week; a small percentage of preschool children may get benefit from 1.25 mg thrice a day.
    • In the largest trial, a multicenter, randomized, placebo-controlled, crossover study of 165 preschool children (age range: 3 to 5.5 years) treated with methylphenidate 3.75 to 30 mg per 24 hours in 3 divided doses, significant improvements both statistically and clinically in ADHD scores were reported with doses of 2.5 mg, 5 mg, and 7.5 mg thrice daily. In some patients (n=7 [4%]), dose titration to 10 mg thrice daily was necessary; the mean effective total daily dose: 14.2 ± 8.1 mg per 24 hours.
    • Although methylphenidate use improved ADHD scores both statistically and clinically, the effect size was smaller with this younger patient population than that seen in school-age children.
    • According to the 10-month continuation phase trial continued or stable clinical improvement was seen at a mean dose of 19.98 mg/day at month 10.

  • Children ≥6 years and Adolescents:

    • Initial: 2.5 to 5 mg p/o two times a day administered before breakfast and lunch; dose should be increased by 5 to 10 mg per 24 hours at weekly intervals; some patients may require 3 doses per 24 hours (eg, additional dose after school) to a usual maximum daily dose of 60 mg per 24 hours, the dose should not exceed 2 mg/kg/ per 24 hours; however, a daily dose of up to 100 mg per 24 hours may be required and tolerated in some patients weighing >50 kg(along with frequent monitoring).

• Extended-release, sustained-release, and long-acting products:

  • Aptensio XR:

    • Children ≥6 years and Adolescents:

      • Initial: 10 mg p/o once daily in the morning; dose may be titrated in 10 mg increments at weekly intervals; maximum daily dose: 60 mg per 24 hours

  • Concerta:

    • Children ≥6 years and Adolescents:

      • Methylphenidate-naive patients: Initial: 18 mg p/o once a day
      • Patients currently using immediate-release methylphenidate: Initial dose: Dosing based on current regimen and clinical judgment; suggested dosing listed below, monitor closely with any therapy change:

    • Switching from methylphenidate immediate release 5 mg 2 to 3 times daily:

      • Concerta 18 mg once a day

    • Switching from methylphenidate immediate release 10 mg 2 to 3 times daily:

      • Concerta 36 mg once a day

    • Switching from methylphenidate immediate release 15 mg 2 to 3 times daily:

      • Concerta 54 mg once a day

    • Switching from methylphenidate immediate release 20 mg 2 to 3 times daily:

      • Concerta 72 mg once a day

    • Dosage adjustment:

      • May increase by Concerta 18 mg per 24 hours increments at weekly intervals to effect not to exceed the following maximum daily dose for age. Note: 27 mg dosage strength is available for situations in which a dosage between 18 and 36 mg is desired.

    • Maximum daily dose of Concerta:

      • Children 6 to 12 years:

        • Usual maximum daily dose: 54 mg per 24 hours;

      • Adolescents:

        • Usual maximum daily dose: 72 mg per 24 hours; however, daily doses up to 108 mg per 24 hours may be required and tolerated in some patients .

  • Cotempla XR-ODT:

    • Children ≥6 years and Adolescents ≤17 years:

      • Initial: 17.3 mg p/o once a day in the morning; may be titrated in 8.6 or 17.3 mg increments at weekly intervals; maximum daily dose: 51.8 mg per 24 hours

  • Jornay PM:

    • Children ≥6 years and Adolescents:

      • Initial: 20 mg p/o once a day in the evening between 6:30 and 9:30 PM (eg, 8:00 PM); may be increased in increments of 20 mg per 24 hours at weekly intervals; maximum daily dose: 100 mg per 24 hours.

Note: If conversion from another methylphenidate formulation is required, the previous formulation should be discontinued and titrated Jornay PM using the above schedule; should not be substituted on a milligram-per-milligram basis.

• Metadate CD:

  • Children ≥6 years and Adolescents:

    • Initial: 20 mg p/o once a day; may be increased by 10 to 20 mg per 24 hours increments at weekly intervals; usual maximum daily dose: 60 mg per 24 hours; however, a daily dose of up to 100 mg per 24 hours may be required and tolerated in some patients weighing >50 kg(along with frequent monitoring).

• Metadate ER, Ritalin-SR:

  • Children ≥6 years and Adolescents:

    • Replace immediate-release tablets when the 8-hour dosage corresponds to sustained-/extended-release tablet size; May administer Ritalin SR once or twice a day. Usual maximum daily dose: 60 mg per 24 hours; however, a daily dose of up to 100 mg per 24 hours may be required and tolerated in some patients weighing >50 kg(along with frequent monitoring).

• QuilliChew ER:

  • Children ≥6 years and Adolescents:

    • Initial: 20 mg p/o once a day in the morning; may be adjusted in 10, 15, or 20 mg increments at weekly intervals (tablets are scored and may be broken in half to achieve dose) to a maximum daily dose of 60 mg per 24 hours.

Note: If conversion from another methylphenidate formulation is required, the previous formulation should be discontinued and titrated Jornay PM using the above schedule; should not be substituted on a milligram-per-milligram basis.​​​​​​​

• Quillivant XR:

  • Children ≥6 years and Adolescents:

    • Initial: 20 mg p/o once a day in the morning; may increase by 10 to 20 mg per 24 hours increments at weekly intervals to a maximum daily dose of 60 mg per 24 hours.

• Ritalin LA:

  • Children ≥6 years and Adolescents:

    • Methylphenidate-naive patients: Initial: 20 mg p/o once a day; may increase by 10 mg per 24 hours increments at weekly intervals; usual maximum daily dose: 60 mg per 24 hours; however, a daily dose of up to 100 mg per 24 hours may be required and tolerated in some patients weighing >50 kg(along with frequent monitoring).

Note: If a lower initial dose is desired, patients may begin with Ritalin LA 10 mg once a day. Alternatively, patients may start therapy with an immediate-release product, and switch to Ritalin LA once immediate-release dosage is titrated to 5 mg twice daily (see below).

• Patients currently receiving immediate-release methylphenidate: Should use the same total daily dose of Ritalin LA.
• Patients currently receiving methylphenidate sustained release (SR): Should use the same total daily dose of Ritalin LA.

Canadian labeling:​​​​​​​

• Concerta:

  • Children ≥6 years and Adolescents:

    • Sustained-release methylphenidate [Canadian product] to Concerta: Oral:

      • Switching from methylphenidate SR 20 mg daily: Concerta 18 mg p/o once daily in the morning
      • Switching from methylphenidate SR 40 mg daily: Concerta 36 mg p/o once daily in the morning
      • Switching from methylphenidate SR 60 mg daily: Concerta 54 mg p/o once daily in the morning

• Biphentin [Canadian product]:

  • Children ≥6 years and Adolescents:

    • Methylphenidate naive patients: Initial: 10 to 20 mg p/o once daily; may adjust in 10 mg increments at weekly intervals; maximum daily dose: 60 mg per 24 hours.

Note: Some children and adolescents may necessarily require the higher doses; should not exceed 1 mg/kg per 24 hours or the adult maximum of 80 mg per 24 hours; close monitoring should be done for adverse events, dose should be reduced or discontinued if adverse events occur.

• Patients currently receiving immediate-release methylphenidate: Use equivalent total daily dose administered once a day.

Topical: Transdermal patch (Daytrana):​​​​​​​

• Children and Adolescents 6 to 17 years:

  • Initial: 10 mg (12.5 cm ) patch once a day; should be applied to hip 2 hours before effect is needed and should be removed 9 hours after application (eg, 3 hours before bedtime); dose titration should be done based on response and tolerability; may increase to next transdermal patch dosage size no more frequently than every week.
  • May remove the patch before 9 hours if a shorter duration of action is required or if late-day adverse effects appear or it may be used for up to 16 hours in the case extended duration of effects are needed.
  • Plasma concentrations usually decline after the patch is removed but absorption of the drug may continue for several hours.

Note: According to manufacturer labeling, patients who are converting from an oral methylphenidate formulation to the transdermal patches should start at 10 mg regardless of the previous dose. The transdermal formulation's bioavailability is different so it is recommended that they be titrated according to their needs. Some clinicians recommend that patients who are converting from oral methylphenidate doses greater than 20 mg per 24-hours should be given higher starting patches. For example, the 15-mg (18.75 cm), the patch was found to have the same effect on 22.5 mg daily (Concerta), 27 mg daily (Concerta), and 20 mg daily (encapsulated beads).

Approximate oral methylphenidate equivalents, with a 9-hour patch wear time, for the 20 mg and 30 mg patches are (Arnold 2007):

Approximate oral equivalent daily dose
Patch size (Daytrana)	Immediate release (mg/day)	Osmotic release (eg,Concerta) (mg/day)
15 mg(18.75 cm2)	22.5	27
20 mg (25 cm )	30	36
30 mg (37.5 cm )	45	54

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Methylphenidate (Ritalin) Use in the Narcolepsy:

• Children ≥6 years and Adolescents:

  • Immediate-release tablets and oral solution (Methylin, Ritalin):

    • Initial: 5 mg p/o two times a day given before breakfast and lunch; should be increased by 5 to 10 increments mg per 24 hours at weekly intervals; twice or thrice daily to a maximum daily dose of 60 mg per 24 hours (in 2 to 3 divided doses)

  • Extended-/sustained-release tablets (Metadate ER, Ritalin-SR):

    • May give in place of immediate-release products, once the immediate-release formulation daily dose is titrated and the titrated 8-hour dosage corresponds to sustained- or extended-release tablet size to a maximum daily dose of 60 mg per 24 hours.

Pregnancy Risk Category: C

​​​​​​​

• There are limited data available on the use of methylphenidate during pregnancy in women with attention deficit/ hyperactivity disorder and narcolepsy. The outcome data is inconsistent.
• If ADHD is a concern in your pregnancy, you may consider taking methylphenidate.
• Monitoring of the effects of methylphenidate on infants and pregnant women is ongoing.
• The National Pregnancy Register for Psychostimulants is available at 1-866-961-2388.

Methylphenidate use during breastfeeding:

• Breast milk contains methylphenidate.
• The relative infant dose (RID), of methylphenidate is 0.7%.
• It is calculated by using the highest concentration of breast milk and compared with a maternal dose of 52mg per 24 hours.
• If the RID of a medication falls below 10%, breastfeeding is generally acceptable.
• According to some sources, breastfeeding is only recommended if the RID for psychotropic drugs is lower than 5%.
• The RID calculation for methylphenidate was performed using a milk content of 19 mg/L. This provides an absolute infant dose via breastmilk of 2.9 mg/kg every 24 hours.
• After three mothers were given methylphenidate for ADHD, the milk concentration was determined.
• The maternal dose ranged between 35 and 80 mg every 24 hours.
• A case report showed that methylphenidate in breast milk was not detectable after 20-21 hours following the administration of the immediate-release tablet.
• Three cases did not report adverse events. However, infants in two cases were older (6 and 11 months) and had limited exposure.
• Long-term developmental effects have not been studied.
• One child was able to grow normally and develop medically up to the age of one year.
• According to the manufacturer, it is important to consider the risks to the infant as well as the benefits to the mother when deciding whether to continue breastfeeding or not during therapy.
• Monitor breastfeeding infants for any adverse reactions such as agitation or anorexia.

Dose in Kidney Disease:

Oral:

• No dosage adjustments provided in the manufacturer's labeling (has not been studied); extensively metabolized to a renally eliminated metabolite with little or no pharmacologic activity.

Transdermal:

• No dosage adjustments are provided in the manufacturer's labeling (has not been studied).

Dose in Liver disease:

Oral:

• No dosage adjustments are provided in the manufacturer's labeling (has not been studied).

Transdermal:

• No dosage adjustments are provided in the manufacturer's labeling (has not been studied).

Common Side Effects of Methylphenidate (Ritalin):

• Central Nervous System:

  • Insomnia
  • Headache
  • Irritability

• Gastrointestinal:

  • Decreased Appetite
  • Xerostomia
  • Nausea

Less Common Side Effects Of Methylphenidate (Ritalin):

• Cardiovascular:

  • Tachycardia
  • Palpitations
  • Increased Blood Pressure
  • Increased Heart Rate

• Central Nervous System:

  • Emotional Lability
  • Anxiety
  • Increased Diastolic Blood Pressure
  • Tics
  • Dizziness
  • Psychomotor Agitation
  • Depressed Mood
  • Nervousness
  • Restlessness
  • Aggressive Behavior
  • Agitation
  • Depression
  • Hypertonia
  • Lack Of Emotion
  • Vertigo
  • Confusion
  • Sedation
  • Tension
  • Tension Headache
  • Paresthesia

• Dermatologic:

  • Hyperhidrosis
  • Excoriation
  • Skin Rash

• Endocrine & Metabolic:

  • Weight Loss
  • Decreased Libido

• Gastrointestinal:

  • Vomiting
  • Abdominal Pain
  • Upper Abdominal Pain
  • Anorexia
  • Bruxism
  • Dyspepsia
  • Motion Sickness
  • Constipation

• Hematologic & Oncologic:

  • Bruise

• Neuromuscular & Skeletal:

  • Back Pain
  • Tremor

• Ophthalmic:

  • Blurred Vision
  • Eye Pain

• Respiratory:

  • Nasopharyngitis
  • Streptococcal Pharyngitis
  • Cough
  • Upper Respiratory Tract Infection
  • Oropharyngeal Pain

• Miscellaneous:

  • Fever

Frequency of side effects not defined:

• Cardiovascular:

  • Cardiac Arrhythmia
  • Decreased Blood Pressure
  • Decreased Pulse
  • Heart Murmur
  • Hypertension
  • Increased Pulse

• Central Nervous System:

  • Drug Abuse
  • Drug Dependence
  • Gilles De La Tourette Syndrome
  • Hypervigilance
  • Jitteriness
  • Mood Changes
  • Outbursts Of Anger
  • Panic Attack
  • Sleep Disorder
  • Toxic Psychosis

• Dermatologic:

  • Macular Eruption

• Endocrine & Metabolic:

  • Growth Suppression
  • Hot Flash
  • Increased Thirst

• Gastrointestinal:

  • Abdominal Distress
  • Diarrhea

• Genitourinary:

  • Erectile Dysfunction

• Hematologic & Oncologic:

  • Anemia
  • Leukopenia

• Hepatic:

  • Increased Serum Alanine Aminotransferase

• Neuromuscular & Skeletal:

  • Asthenia
  • Muscle Spasm

• Ophthalmic:

  • Dry Eye Syndrome

• Respiratory:

  • Dyspnea
  • Sinusitis

Contraindications to Methylphenidate (Ritalin):

US labeling

• Hypersensitivity to methylphenidate and any other component of the formulation (e.g. angioedema, allergic reactions)
• Use within or after 14 days of MAOI therapy

Additional contraindications include: Concerta. Daytrana. Metadate CD. Methylin. Metadate ER.

• Anxiety, tension, and agitation.
• Glaucoma
• Tourette syndrome, tics or family history

Meta:

• Hypertension severe
• Heart failure
• Arrhythmia
• Hyperthyroidism and thyrotoxicosis
• Recent MI or angina
• Use of halogenated anesthetics in conjunction
• Rare hereditary issues of fructose intolerance, glucose -galactase malabsorption or sucrose-isomaltase deficiency in patients with rare cases

Canadian labeling:

• Hypersensitivity to methylphenidate and any other component of the formulation
• Anxiety, tension, and agitation.
• Glaucoma
• Use within or after 14 days of MAO inhibitor therapy
• Tourette syndrome, tics or family history (except Concerta)
• Thyrotoxicosis
• Advanced arteriosclerosis
• Cardiovascular disease symptoms
• Moderate to severe hypertension

Additional contraindications Foquest:

• Hypersensitivity to sympathomimetic drugs or known hypersensitivity
• Histories of drug abuse

Ritalin and Ritalin-SR:

• Pheochromocytoma

Warnings and precautions

• Cardiovascular events

  • Children and adolescents who have preexisting structural heart abnormalities can die suddenly from CNS stimulant therapy.
  • Adults with MI, sudden death, stroke and death from such treatment have also been reported.
  • A large retrospective cohort study that included 1,200,438 children and adolescents (aged 2-24 years) who were prescribed methylphenidate or dexmethylphenidate as well as dextroamphetamines, amphetamine salts or pemoline found no evidence of ADHD medication use increasing the risk for stroke, sudden cardiac death, acute MI or stroke.
  • Patients with known structural cardiac abnormalities, cardiomyopathy or serious heart rhythm abnormalities should avoid stimulants.
  • Some products are not recommended for use if you have angina, heart disease, severe hypertension, recent MI, arrhythmias or heart failure.
  • Before starting any stimulant, it is important to review your medical history and the family history of sudden death.
  • For assessment of cardiac disease, a physical exam should be done
  • If you find evidence of cardiac disease, such as an echocardiogram or ECG, further evaluation is necessary.
  • Patients who experience exertional chest pain, unexplained systolic symptoms, or other signs of cardiac disease should have a prompt cardiac evaluation.

• Hypersensitivity

  • Hypersensitivity reactions such as angioedema or anaphylactic reactions may occur.

• Peripheral vasculopathy:

  • The use of stimulants may cause peripheral vasculopathy.
  • These symptoms, which include Raynaud phenomenon and milder, are often intermittent and temporary. Symptoms generally improve upon discontinuation or reduction in dose.
  • The effects of peripheral vasculopathy on the periphery have been documented at various times and at therapeutic doses in all ages.
  • It is rare for it to cause soft tissue or digital ulceration. Monitoring should be done during therapy for any digital changes and referrals should be made for further evaluation (eg rheumatology).

• Priapism

  • Patients with pediatric and adult patients have reported prolonged (more than four hours), painless, and sometimes painful erections.
  • Prapism can develop after prolonged use of drugs, including after an increase in dosage or during withdrawal.
  • Patients with certain hematological disorders (eg, sickle cells disease, malignancies or perineal trauma) may be at greater risk.
  • Patients who experience painful, prolonged or persistent erections should immediately seek medical attention.
  • For severe cases, get an emergent urological consultation,
  • There is a strong association between Priapism and different products and dosage forms. It is not known if there will be recurrence if you re-challenge with another formulation.
  • Avoid stimulants and atomoxetine in patients suffering from severe priapism.

• Visual disturbance:

  • Stimulants can cause blurred vision and difficulty in accommodation.

• Potential for abuse: [US Boxed Warning]

  • There is a high potential for abuse and dependence with the use of CNS stimulants, including methylphenidate-containing products and amphetamines.
  • Before prescribing, it is important to assess the risk of abuse. Also, monitor for signs of abuse or dependence during therapy.
  • Long-term abuse may lead to psychological dependence and marked tolerance.
  • Frequent psychotic episodes may occur, particularly if there is parenteral abuse.
  • Abusing substances can lead to severe depression, so it is important to be vigilant.
  • Long-term therapeutic use can lead to withdrawal, which may result in the unmasking of symptoms that could be underlying the disorder. This may need follow-up.

• Cardiovascular disorders:

  • CNS stimulants may increase blood pressure and heart rate. In pediatric patients, the mean increase in heart beat was 3 to 6 BPM and blood pressure was 2 - 4 mm Hg.
  • Patients with heart disease, hypertension, heart failure, recent MI and ventricular arrhythmia should exercise caution when using this medication.
  • Certain products should not be used if you have severe hypertension, hyperthyroidism or angina.

• Psychiatric disorders

  • Patients with preexisting psychosis should be cautious as it may exacerbate symptoms of behaviour and thought disorder or bipolar disorder. It could also cause mixed/manic episodes.
  • The use of stimulants can lead to new-onset psychosis and mania.
  • Screen patients for bipolar disorder before starting treatment. If psychotic or manic symptoms occur (e.g., delusional thinking and hallucinations), discontinue treatment.
  • It is important to monitor closely as aggressive behavior and hostility in children can be caused by it (causal relationship not established).
  • Patients with ADHD may have an increased risk of suicide attempts and suicidal thoughts.
  • However, large cohort studies have not shown a causal relationship between ADHD and methylphenidate.
  • Suicide-related behavior should be monitored.

• Seizure disorder:

  • Patients with seizure disorders should exercise caution when using this medication.
  • It may result in a lower seizure threshold, which could lead to seizure activity that is sudden or unexpected.
  • Stop use if seizures develop.

• Tourette syndrome/tics:

  • Patients with Tourette syndrome and other tic disorders should exercise caution when using this product.
  • Stimulants may exacerbate Tourette syndrome and motor and phonic tics. However, there is limited evidence to support an increase in tics.
  • Before starting therapy, it is important to evaluate Tourette syndrome and Tics.

Methylphenidate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Antacids	May increase the absorption of Methylphenidate. Specifically, antacids may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption.
Antihypertensive Agents	Methylphenidate may diminish the antihypertensive effect of Antihypertensive Agents.
Anti-Parkinson Agents (Dopamine Agonist)	Methylphenidate may enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist).
Antipsychotic Agents	May enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents.
AtoMOXetine	May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics.
BuPROPion	May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential.
Cannabinoid-Containing Products	May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol.
CloNIDine	Methylphenidate may enhance the adverse/toxic effect of CloNIDine.
Doxofylline	Sympathomimetics may enhance the adverse/toxic effect of Doxofylline.
Esketamine	May enhance the hypertensive effect of CNS Stimulants.
Fosphenytoin	Methylphenidate may increase the serum concentration of Fosphenytoin.
Guanethidine	May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics.
Histamine H2 Receptor Antagonists	May increase the absorption of Methylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extendedrelease capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption.
Ioflupane I 123	Methylphenidate may diminish the diagnostic effect of Ioflupane I 123.
PHENobarbital	Methylphenidate may increase the serum concentration of PHENobarbital.
Phenytoin	Methylphenidate may increase the serum concentration of Phenytoin.
Primidone	Methylphenidate may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations could become elevated. Methylphenidate may increase the serum concentration of Primidone.
Proton Pump Inhibitors	May increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption.
Serotonin Modulators	Methylphenidate may enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased.
Solriamfetol	Sympathomimetics may enhance the hypertensive effect of Solriamfetol.
Solriamfetol	CNS Stimulants may enhance the hypertensive effect of Solriamfetol.
Sympathomimetics	May enhance the adverse/toxic effect of other Sympathomimetics.
Tricyclic Antidepressants	Methylphenidate may enhance the adverse/toxic effect of Tricyclic Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants.
Vitamin K Antagonists (eg, warfarin)	Methylphenidate may increase the serum concentration of Vitamin K Antagonists.
Risk Factor D (Consider therapy modification)
Cocaine (Topical)	May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use.
Iohexol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iomeprol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iopamidol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Risk Factor X (Avoid combination)
Acebrophylline	May enhance the stimulatory effect of CNS Stimulants.
Alcohol (Ethyl)	May enhance the adverse/toxic effect of Methylphenidate. Alcohol (Ethyl) may increase the serum concentration of Methylphenidate.
Inhalational Anesthetics	Methylphenidate may enhance the hypertensive effect of Inhalational Anesthetics.
Iobenguane Radiopharmaceutical Products	CNS Stimulants may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose.
Monoamine Oxidase Inhibitors	May enhance the hypertensive effect of Methylphenidate.

Monitoring parameters:

• CBC, differential, and platelet counts should be monitored periodically with prolonged use
• Blood pressure
• Pulse rate
• Signs and symptoms of depression, aggression, hostility, suicidal behavior/ideation
• Growth rate (height and weight) in children
• Signs of central nervous system stimulation
• Signs of peripheral vasculopathy (eg, digital changes)

Transdermal:

• Signs of worsening erythema, blistering or edema which does not improve within 48 hours of patch removal, or spreads beyond patch site.
• Detailed evaluation should be done for cardiovascular risk when used for the treatment of ADHD.
• Heart rate & blood pressure should be monitored and an ECG should be obtained before initiation.

How to administer Methylphenidate (Ritalin)?

Oral: Controlled-release capsule (Biphentin and Foquest [Canadian Products]):

• Take the capsules in the morning with a full glass of water (Foquest), or with other liquids (Biphentin). Capsules shouldn't be broken or chewed. 
• You can also open the capsules and sprinkle the contents on yogurt, ice cream or applesauce. However, you must not crush or chew them.
• Foquest should be taken within 10 minutes of the food being sprayed.
• After administration, rinse your mouth with water and then swallow it. If Foquest is not given within 10 minutes after mixing, it should be thrown out.

Immediate-release tablet (Ritalin), IR tablet solution (Methylin), IR chewable tablets (Methylin):

• Take each dose 30 to 45 minutes prior to eating. 
• If you have difficulty sleeping, ensure that your last dose is taken before 6 PM. 
• Take 8 ounces or more of water with each chewable tablet.

Extended-release capsule (Aptensio XR. Jornay PM. Metadate CD. Ritalin LA:

• Give Aptensio XR and Metadate CD in the morning, and Jornay PM at night between 6:30 and 9:30 pm. 
• You can also open the capsules and put a small amount of the contents (equal to one tablespoon) of applesauce on top. 
• The applesauce mixture should not be chewed. You should not crush, chew or divide the capsule contents.

Extended-release, orally disintegrating tablet (CotemplaXR-ODT):

• In the morning, take the tablet with or without food. You should remove the tablet from the blister pack using dry hands.
• Do not push the tablet through foil. You should allow the tablet to dissolve on your tongue without chewing, crushing or squeezing.

Extended-release suspension (QuillivantXR):

• Should be administered in the morning, with or without food. 
• Before administering, shake the bottle for at least 10 seconds. Use the oral dosing device provided; rinse after each use.

Extended-release chewable tablet (QuilliChew ERR):

• Taken with or without food, should be taken in the morning. 
• Tablets can be scored and halved.

Extended-release tablet Metadate ER:

• Take the tablet 30 to 45 minutes before eating. Take the tablet whole and drink water.
• Concerta: Take in the morning. You can take Concerta with or without food.
• However, you must drink water or another fluid. You should not crush, chew, or divide the tablet.

Sustained-release tablet, (Ritalin SR):

• You should swallow the entire tablet whole and not chew or crush it.

Topical: Transdermal (Daytrana):

• Apply to dry, clean, non-oily skin to the hips. Avoid the waistline.
• The patch site should not have been premedicated using hydrocortisone, creams, ointments or emollients.
•  To alternate hips, should be applied daily at the same time.
• To ensure proper adhesion, press the area for 30 seconds. 
• Avoid exposing the application site to heat sources outside.
• This could increase drug absorption. It is best to throw out any patch that has difficulty separating from the liner.
• You should not use a torn or damaged patch. Do not cut the patch. 
• The patch may be removed if it becomes loose. However, the total time of wear should not exceed 9 hours. 
• If the effect lasts for a shorter time or you experience side effects, it is possible to remove the patch quickly.
• After handling the patch, wash your hands with soap and water. 
• Avoid touching the sticky side. Apply an oil-based product to the edges of the patch to ease the process.
• Acetone-based products, such as nail polish remover, should be used to smoothen the edges. 
• You can dispose of the used patch by folding its adhesive side over itself and disposing of it in a container with a lid.

Mechanism of action of Methylphenidate (Ritalin):

It is mildly stimulant to the CNS; causes the blockade in the reuptake norepinephrine/dopamine into presynaptic neuronal neurons; seems to stimulate the cerebral cortex and subcortical structures, just like amphetamines.

Onset of action (AAP 2011): Children: Oral:

• Extended-release formulations (capsule, [Metadate CD], Ritalin LA], tablets[Concerta]: 20-60 minutes
• Instant-release formulations (chewable tablets, oral solution, tablet [Methylin], Ritalin]: 20-60 minutes
• Sustained-release tablet, (Ritalin-SR),: 60 to 180 minutes

Transdermal (Daytrana), 60 minutes

• Adults: Oral: Controlled release: Foquest [Canadian Product]: Within 60 Minutes
• Maximum Effect: Oral: Intimate-release tablet within 2 hours; Sustained release tablet within 4 to 7 hours

Time of action: Oral:

• 16 hours Controlled-release capsule (Foquest [Canadian Product])
• Extended-release capsule Metadate CD, Ritalin La: 6-8 hours (AAP 2011, AptensioXR: =16hrs
• Extended-release tablet (Concerta), 8-12 hours
• Extended-release tablet (Metadate EER): 8 hours
• Instant-release formulations (chewable tablet or oral solution, immediate release tablet [Methylin], Ritalin]: 3 to 5 Hours
• Sustained-release tablet, (Ritalin-SR),: 2-8 hours

Transdermal (Daytrana), 11-12 hours

Absorption:

• Oral: Aborbed easily after oral administration
• Capsule controlled-release:
• Biphentin [Canadian Product]: When given with food, there is a slight delay in the initial peak (18 min); however, immediate-release tablets have a similar AUC in fed and fasted states (100%).
• Foquest [Canadian Product]: AUC, C and sensitivity are not affected by the food

Extended-release capsule

• High-fat meals can increase AptensioXR:C (28%) or AUC (19%). A 40% alcohol level resulted in 96% methylphenidate release within two hours.
• Jornay PM - There is a delay of initial absorption. =5% total drug will be available within the first 10 hours. C (14%) decreased after a high-fat dinner at night, which extended the median time by 2.5 hours. Pharmacokinetics were not affected by a high-fat breakfast. At an alcohol concentration of 40% there was an increase in the rate at which methylphenidate is released. This resulted in 97% being released within 2 hours.
• Metadate CD: High-fat meals caused a delay in peak time (1 hour), as well as an increase in C (30%), and AUC (17%). At an alcohol concentration of 40%, there was an increase in the rate at which methylphenidate is released in the first hour. This resulted in 84% of the methylphenidate being emitted.
• Ritalin LA: High-fat meals caused delays in absorption and peak times. However, this did not affect the initial peak concentration nor the amount absorbed. (second peak lowered to 25%) At an alcohol concentration of 40%, there was a 98% release in the first hour.
• Extended-release chewable tablets: High-fat meals caused an increase of C (20%) & AUC (4%). At an alcohol concentration of 40%, there was an increase in the rate at which methylphenidate is released. This resulted in 90% of the methylphenidate being dissolved.
• Extended-release oral disintegrating tablet: CotemplaXR-ODT: High-fat meals caused a decrease of C (24%) et an increase in AUC (16%), leading to a earlier peak (0.5 hours).
• Extended-release suspension: QuillivantXR: High-fat meals caused an earlier peak (1h00) and an increase of C (28%) as well as AUC (19%).
• Extended-release tablet Metadate ER: Fasting caused a greater increase of C and AUC than food.
• Methylin: An immediate-release chewable tablet. A high-fat meal can cause a delay in peak (1hr) and an increase of AUC (20%).
• Immediate release solution: Methylin - A high-fat meal resulted in a delay of peak time (1hr) and an increase in C (13%) as well as AUC (25%).
• Tablets for immediate release: High-fat meals caused an increase in AUC (25%) & C (27%).
• Transdermal: The skin was more absorbent when it was exposed to heat or inflamed. Continuous absorption was observed for nine hours after application.

Distribution: Vd-methylphenidate: 2.65 +- 1.11 L/kg,l-methylphenidate: 1.80 +- 0.91 L/kg

Protein binding- 10% to 33%

Metabolism: Extensively metabolized, predominately via de-esterification by carboxylesterase CES1A1 to alpha-phenyl-piperidine acetic acid (PPAA; ritalinic acid) which has little to no pharmacologic activity.

Bioavailability:

• Extended-release capsule
• Aptensio XR - 102% (relatively to immediate-release oral products)
• Jornay PM - 73.9% (relatively to immediate-release oral products)
• Extended-release suspension with QuillivantXR: 95% (relatively to immediate-release oral solutions)
• Oral solution and chewable tablets for immediate release: Bioequivalent to immediate tablets
• Sustained-release: 105% (49% - 168%) for children, and 101% (85% – 152%) for adults (relatively to immediate oral product).

Daytrana transdermal patch: Transdermal patch (Daytrana). The 1st pass effect is lower than oral administration. Therefore, lower AUCs can be achieved via transdermal route (on a mg/kg basis).

Half-life elimination: Controlled-release capsule Biphentin [Canadian Product]: Children: 2.4 Hours; Adults : 2.1 Hours; Foquest [Canadian Product]: Adults : 6.95 + 3.25 hours Extended-release capsule

• AptensioXR: Adults: 5 Hours
• Jornay PM - 5.9 Hours
• Metadate CD: Adults 6.8 hours
• Ritalin LA: Children 1.5 to 4 Hours; Adults 3 to 4.2 Hours
• Extended-release chewable tablets: 5.2 Hours
• Extended-release tablet that can be disintegrated orally: 4 to 5 hours
• Extended-release suspension with QuillivantXR: Children >=9 Years, Adults: 5 Hours

Extended-release tablet Concerta: Adults and Adolescents: 3.5 Hours Adults: 3 hours. Immediate-release chewable tablets: Methylin Instant-release solution for Methylin: Adults: 2.75 hours Tablet for immediate release: Children: 3.5 hours (11.5 to 5 hours). Adults can work for 3.5 hours (1.3-7.7 hours). Transdermal: Children and adolescents 6-17 years old: d-methylphenidate 4 to 5 hours, or lmethylphenidate From 1.4 to 2 hours

Time to reach peak: Capsule controlled-release:

• Biphentin [Canadian Product]: Children: Initial: 2.5 Hours; Adults Initial: 2 Hours
• Foquest [Canadian Product]: Adults: First peak at 1.6 hour followed by second peak of 12.5 (range: 11-16 hours).

Extended-release capsule

• Aptensio XR Adults: Initial: 2 Hours; Second Peak: 8 Hours
• Jornay PM: 14 Hours
• Metadate CD for Children: Initial: 1.5 Hours; Second Peak: 4.5 Hours

Ritalin LA

• Children: First peak: 1 to 3 hours. Second peak: 5 to 11.
• Adults: First peak: 1.3 to 4 hrs; Second peak: 43 to 6.5 hrs

Extended-release chewable tablet QuilliChew EMR: 5 hours (median). Extended-release tablet that can be disintegrated orally: CotemplaXR-ODT: 5 Hours Extended-release suspension with QuillivantXR: Children (9-12 years old): 4.05 hours (range 3.98 to 6hrs); Adolescents (11-3 years) 2 hours (range 1.98 to 4hrs); Adults (4 hours) (range 1.3 to 7.7 hours). Extended-release tablet Concerta: Initial time: 1 hour, then gradually increasing concentrations for 5 to 9 hours. Mean peak time: 6 to 10 hours Instant-release chewable tablet Methylin: 1 - 2 hours Instant-release solution for Methylin: 1 - 2 hours Children: 1.9 hours (range 0.3 to 4.4). A high-fat meal causes a quicker time to peak than a low-fat meal (median T: 2.5 hours versus three hours). Children: 4.7 hours Sustained-release Tablet (range: 1.3-8.2 hours). Transdermal: 8-10 hours

Excretion 78% to 97% of the drug is excreted in urine (as unchanged drug and metabolites) and 1% to 33% in feces

International Brand Names of Methylphenidate:

• Aptensio XR
• Concerta
• Cotempla XR-ODT
• Daytrana
• Metadate CD
• Metadate ER
• Methylin
• QuilliChew ER
• Quillivant XR
• Relexxii
• Ritalin
• Ritalin LAACT Methylphenidate ER
• APO-Methylphenidate
• APO-Methylphenidate ER
• APO-Methylphenidate SR
• Biphentin
• Concerta
• Foquest
• PHL-Methylphenidate HCl
• PHL-Methylphenidate
• PMS-Methylphenidate
• PMS-Methylphenidate ER
• RATIO-Methylphenidate
• Ritalin
• Ritalin SR
• SANDOZ Methylphenidate SR
• TEVA-Methylphenidate ER-C
• Adaphen
• Adaphen XL
• Addwize
• Aradix Retard
• Artige
• Attenta
• Cognil
• Comcerta
• Concentra
• Concentra SR
• Concerta
• Concerta LP
• Concerta Oros
• Delmosart
• Equasym
• Equasym Depot
• Equasym
• Retard
• Equasym XL
• Inspiral
• Matoride XL
• Medikinet
• Medikinet CR
• Medikinet MR
• Medikinet Retard
• Medikinet XL
• Metadate CD SR
• Methylin
• Methylphen
• Metidate
• MFD
• Penid
• Phenida
• Prohiper
• Quasym LP
• Rilatine
• Ritalin
• Ritalin LA
• Ritalin
• LP
• Ritalin SR
• Ritalin-SR
• Ritalina
• Ritalina LA
• Ritaline
• Ritaline LP
• Rubifen
• Rubifen
• SR
• Tradea
• Tradea LP
• Xenidate XL

Methylphenidate Brands Names in Pakistan:

Methylphenidate HCl Tablets 10 mg in Pakistan
Fanidan	Danas Pharmaceuticals (Pvt) Ltd
Fanidan	Danas Pharmaceuticals (Pvt) Ltd
Leadophen	Leads Pharma (Pvt) Ltd
Madalin	Mediate Pharmaceuticals (Pvt) Ltd
Methril	Bryon Pharmaceuticals (Pvt) Ltd.
Phenida	Zafa Pharmaceutical Laboratories (Pvt) Ltd.
Rilen	Gray`S Pharmaceuticals
Rital	Aries Pharmaceuticals (Pvt) Ltd
Ritalin	Novartis Pharma (Pak) Ltd

Methylphenidate HCl Tablets 100 mg in Pakistan
Evigil	English Pharmaceuticals Industries

Methylphenidate HCl Tablets 200 mg in Pakistan
Evigil	English Pharmaceuticals Industries