Methylphenidate – Side Effects and Dosage

Background

Methylphenidate is a central nervous system stimulant used most commonly in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and for narcolepsy. Also known as the marketed products Ritalin, Concerta, or Biphentin, methylphenidate is used with other treatment modalities (psychological, educational, cognitive behaviour therapy, etc) to improve the following group of developmentally inappropriate symptoms associated with ADHD: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. Long-acting formulations of psychostimulants such as methylphenidate, Dextroamphetamine, and Lisdexamfetamine are considered the most effective and widely used treatment for ADHD, and are considered first-line options for children, adolescents, and adults as recommended by CADDRA (Canadian ADHD Resource Alliance). 12 CADDRA recommends the use of methylphenidate due to long term studies, of over twenty years in duration, which show methylphenidate is safe and effective.

Properties and Characteristics of Methylphenidate

Drug class	Central nervous system (CNS) stimulants
Brand Names	Adhansia, Aptensio, Biphentin, Concerta, Cotempla, Daytrana, Foquest, Jornay, Metadate, Methylin, Quillichew, Quillivant, Relexxii, Ritalin
Synonyms	Methyl phenidylacetate, Methylphenidan, Methylphenidate, Methylphenidatum, Metilfenidato
Molecular Formula	C14H19NO2
Molecular Weight	233.31 g/mol
IUPAC Name	methyl 2-phenyl-2-piperidin-2-ylacetate
Structural formula of main components
Pure active ingredient	Methylphenidate
Appearance	Crystals
Melting point	74-75 °C
Solubility	Practically insoluble in water and Soluble in alcohol, ethyl acetate, ether
Excretion	Excreted in the urine as ritalinic acid (60%-86%)
Storage	Store these tablets at room temperature of 77°F (25°C)
Available Forms	Capsule
Prescription	Doctor prescription is required

What is Methylphenidate (Ritalin) used for?

• Attention deficit-hyperactivity disorder (ADHD)
• Narcolepsy (daytime sleepiness)

What are the side effects of Methylphenidate (Ritalin)?

Serious Side Effects

Contact your healthcare provider immediately if you experience any of the following.

• Painful erections lasting longer than 4 hours (also known as priapism)
• Serious heart problems
• Unexplained wounds appearing on fingers or toes

The following side effects may get better over time as your body gets used to the medication. Let your healthcare provider know immediately if you continue to experience these symptoms or if they worsen over time.

Common Side Effects

• Fast heart rate
• Headache
• Trouble sleeping
• Anxiety
• Excessive sweating
• Weight loss
• Decreased hunger
• Dry mouth
• Nausea
• Stomach pain
• High blood pressure

Mechanism of action

While its exact mechanism is unclear, methylphenidate (MPH) has been shown to act as a norepinephrine and dopamine reuptake inhibitor (NDRI), thereby increasing the presence of these neurotransmitters in the extraneuronal space and prolonging their action. There is a dose-related effect of psychostimulants on receptor stimulation, where higher doses are shown to increase norepinephrine (NE) and dopamine (DA) efflux throughout the brain which can result in impaired cognition and locomotor-activating effects. In contrast, low doses are found to selectively activate NE and DE neurotransmission within the prefrontal cortex which is an area of the brain thought to play a prominent role in ADHD pathophysiology, thereby improving clinical efficacy and preventing side effects. The lower doses used to treat ADHD are not associated with the locomotor-activating effects associated with higher doses and instead reduce movement, impulsivity, and increase cognitive function including sustained attention and working memory. Methylphenidate’s beneficial effects in sustaining attention have also been shown to be mediated by alpha-1 adrenergic receptor activity.

Clinical findings have shown that children with ADHD have an abnormality in the dopamine transporter gene (DAT1), the D4 receptor gene (DRD-4), and/or the D2 receptor gene that may be at least partly overcome by the dopaminergic effects of methylphenidate, suggesting a possible mode of action.

What may interact with this medication?

Do not take this medication with any of the following:

• Lithium
• MAOIs like Carbex, Eldepryl, Marplan, Nardil, and Parnate
• Other stimulant medications for attention disorders, weight loss, or to stay awake
• Procarbazine

This medication may also interact with the following:

• Atomoxetine
• Caffeine
• Certain medications for blood pressure, heart disease, irregular heart beat
• Certain medications for depression, anxiety, or psychotic disturbances
• Certain medications for seizures like carbamazepine, phenobarbital, phenytoin
• Cold or allergy medications
• Warfarin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For attention deficit hyperactivity disorder (ADHD)

For short-acting oral dosage forms (chewable tablets or solution):

• Adults—Administer 2 or 3 times a day and take 30 to 45 minutes before meals. The average dose is 20 to 30 milligrams (mg) per day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children 6 years of age and older—At first, 5 mg 2 times a day, taken before breakfast and lunch. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

For short-acting oral dosage form (tablets):

• Adults—20 to 30 milligrams (mg) given in divided doses 2 or 3 times a day, taken 30 to 45 minutes before meals. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children 6 years of age and older—At first, 5 mg 2 times a day, taken before breakfast and lunch. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

For long-acting oral dosage form (extended-release capsules):

Patients who have not been treated with methylphenidate

Adhansia XR®:

• Adults and children 6 years of age and older—At first, 25 milligrams (mg) once a day, taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 100 mg per day for adults and 85 mg for children.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

Aptensio XR™, Metadate CD®, Ritalin LA®:

• Adults and children 6 years of age and older—At first, 10 to 20 milligrams (mg) once a day, taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

Patients who are already taking methylphenidate

• Adults and children 6 to 12 years of age—10 to 60 milligrams (mg) once a day, taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

For long-acting oral dosage form (extended-release suspension):

• Adults and children 6 years of age and older—At first, 20 milligrams (mg) once a day, taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

For long-acting oral dosage form (extended-release chewable tablets):

• Adults and children 6 years of age and older—At first, 20 milligrams (mg) once a day, taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

For long-acting oral dosage form (extended-release disintegrating tablets):

• Adults and children 6 years of age and older—At first, 17.3 milligrams (mg) once a day, taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 51.8 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

For long-acting oral dosage form (extended-release tablets):

Patients who have not been treated with methylphenidate

• Adults—At first, 18 to 36 milligrams (mg) once a day in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 72 mg per day.
• Teenagers 13 to 17 years of age—At first, 18 mg once a day in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 72 mg per day.
• Children 6 to 12 years of age—At first, 18 mg once a day in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 54 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by your doctor.

Patients already using methylphenidate

• Adults and children 6 years of age and older—At first, 18 to 72 milligrams (mg) once a day in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 72 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by your doctor.

For narcolepsy

For short-acting oral dosage forms (chewable tablets or solution):

• Adults—Administer 2 or 3 times a day and take 30 to 45 minutes before meals. Average dose is 20 to 30 milligrams (mg) per day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children 6 years of age and older—At first, 5 mg 2 times a day, taken before breakfast and lunch. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by the doctor.

For short-acting oral dosage form (tablets):

• Adults—20 to 30 milligrams (mg) given in divided doses 2 or 3 times a day, taken 30 to 45 minutes before meals (breakfast and lunch). Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children 6 years of age and older—At first, 5 mg 2 times a day, taken before breakfast and lunch. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
• Children younger than 6 years of age—Use and dose must be determined by your doctor.

Symptoms of a Methylphenidate Overdose

Taking Methylphenidate if it is not prescribed for you, or taking more than the doctor-recommended dose, can cause the drug to be habit-forming. Abuse of Methylphenidate can lead to overdose. Methylphenidate overdose symptoms range from moderate to severe, depending on the amount of Methylphenidate ingested, and if other drugs have been taken with it. These symptoms may include:

• Dry mouth and nose
• Vomiting
• Tremors
• Muscle twitching
• Agitation
• Seizure
• Hallucinations
• Confusion
• Increased heartbeat
• Palpitations
• Sweating
• Blurred vision
• Fainting
• Irritability

The severity of acute Methylphenidate overdose symptoms will be greater if Methylphenidate has been taken in large doses, and these symptoms typically occur in a progression, beginning with restlessness, agitation, and irritability and elevating to physical symptoms such as rapid heart rate and convulsions.

What precautions are associated with Methylphenidate?

Store methylphenidate in a secure place out of the reach of children, and at room temperature. Do not share your methylphenidate prescription with anyone, even someone with ADHD. Sharing prescription medication is illegal and can cause harm.

You should not take methylphenidate if you have any of the following conditions: allergy or hypersensitivity to methylphenidate HCI or any of the ingredients in methylphenidate medications, anxiety/agitation, glaucoma, tics or history of Tourette’s syndrome (There is conflicting evidence regarding if tics can get better, stay the same or get worse with stimulant treatment for ADHD), or if you are taking monoamine oxidase inhibitors (MAOIs).

Chewable tablets can contain phenylalanine, and can be harmful to people with phenylketonuria.

You should use caution while taking methylphenidate if you have a history of heart or circulation problems.

If you’re thinking of becoming pregnant, discuss the use of methylphenidate with your doctor. Animal studies indicate a potential risk of fetal harm but no harm has been found in human beings. Methylphenidate is passed through breastmilk but the effects of ADHD medications in breast milk have never been studied.  The American Association of Pediatrics recommends that mothers do not nurse while taking methylphenidate “out of an abundance of caution.”