Overview:
Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric childhood disorder. Methylphenidate hydrochloride comes under the class of drugs known as central nervous system (CNS) stimulants that act by altering the amounts of some natural substances in the brain. The biologically active form of the compound is piperidine and the d-threo isomer. The compound comes in various short-acting and long-acting preparations. Every preparation has a different delivery system with distinct kinetics. The compound usually increases the synaptic dopamine concentration.
The sustained-release and immediate-release preparations of Methylphenidate hydrochloride are efficiently used in children and adults with attention deficit hyperactivity disorder. The mechanism of action usually involves norepinephrine and monoamines dopamine. The adverse effects of this drug include appetite disturbance, insomnia, headache, stomach ache, and dizziness.
Indications:
FDA- approved indications include
-
Attention deficit hyperactivity disorder (ADHD) in children and adults.
-
Second-line treatment for narcolepsy in adults.
Non- FDA approved indications (off-label uses) include
-
Treatment for fatigue in patients with cancer.
-
Refractory depression in the geriatric population.
-
Enhancing cognitive performance.
These indications are still being researched and newly adapted into clinical practice.
What Is Attention Deficit Hyperactivity Disorder (ADHD)?
Attention deficit hyperactivity disorder is an amalgamation of several problems, like hyperactivity, difficulty sustaining attention, and impulsive behavior.
ADHD may also lead to troubled relationships, low self-esteem, and performance in school. Sometimes the symptoms decrease with age, but in some cases, the symptoms of ADHD never disappear completely. Various strategies are adopted to overcome these symptoms and lead a normal life.
Warning:
Methylphenidate hydrochloride can be addictive. Hence, large doses of this drug must be avoided. The patient must not take the drug more frequently or longer. If too much Methylphenidate is taken, unusual alteration in behavior is experienced. The patients must inform the doctor about the consumption of large amounts of alcohol in the past or the use of street drugs and must not stop the use of Methylphenidate without consulting a doctor, particularly if the medication has been overused. The doctor usually decreases the dose gradually and monitors the patient carefully. Methylphenidate must be stored safely to avoid accidental usage.
For Patients:
Why Is Methylphenidate Hydrochloride Prescribed?
Methylphenidate hydrochloride treats attention deficit hyperactivity disorder (ADHD), which causes difficulty controlling actions, focusing, and remaining quiet or still. Methylphenidate hydrochloride can also treat narcolepsy, a condition that causes excessive sleepiness during the day and sudden sleep attacks.
How Is Methylphenidate HCl Used?
Methylphenidate HCl is available in the following forms:
-
Immediate-release tablet.
-
Chewable tablet.
-
Long-acting (extended-release) suspension (liquid).
-
Intermediate-acting (extended-release) tablet.
-
Long-acting (extended-release) capsule.
-
Long-acting (extended-release) tablet.
-
Long-acting (extended-release) chewable tablet.
-
Long-acting (extended-release) orally disintegrating tablet.
A certain amount of medication is released immediately by orally disintegrating tablets, long-acting tablets, and capsules. The remaining drug is released steadily over a certain period.
All the above forms of Methylphenidate hydrochloride are taken orally. The chewable tablets, regular tablets, and solution are usually taken twice or thrice daily by adults and twice daily by children, usually 35 to 40 minutes before meals.
Adults taking three doses of this medication must take the last dose before six o’clock in the evening to avoid difficulty in falling asleep or staying asleep.
-
Intermediate-Acting Tablets: Once or twice daily, in the morning or early afternoon, 30 to 45 minutes before a meal.
-
Long-Acting Capsule: Once daily before breakfast.
-
Long-Acting Tablet, Long-Acting Chewable Tablet, Long-Acting Suspension, and Long-Acting Capsules: Daily once in the morning with or without food.
-
Long-Acting Suspension: Acts sooner if it is taken with food.
-
Long-Acting Orally Disintegrating Tablet and the Long-Acting Capsule: Daily once in the morning and must be taken consistently, with or without food.
-
Long-Acting Capsule: Once daily in the evening, and must be taken consistently, simultaneously in the evening, and with or without food.
This medication must be taken as directed by the physician. The extended-release orally disintegrating tablet must not be pushed through the blister pack foil, and the foil packaging must be peeled back with dry hands. The tablet should be taken out and placed immediately in the mouth. This helps dissolve the tablet quickly through the saliva without needing water.
The immediate-release chewable tablets must be chewed thoroughly, followed by a glass of water or other liquid. If taken without enough liquid, the tablet might swell and obstruct or choke the throat in case of vomiting, chest pain, and difficulty swallowing or breathing after taking the chewable tablet. The doctor must be informed immediately.
The intermediate-acting and long-acting tablets and capsules must be swallowed whole without splitting, chewing, or crushing. If these capsules cannot be swallowed as a whole, the contents of the capsule can be sprinkled in a tablespoon of yogurt or applesauce, and the mixture can be consumed immediately, followed by a glass of water.
Precautions:
Allergies:
The patient should inform the doctor about allergies to this drug, any other medications like Aspirin, tartrazine dye, or any other ingredients in the Methylphenidate hydrochloride product that the patient is taking. The doctor should also be informed about other allergies, like allergies to foods, preservatives, dyes, or animals. The patient should be aware of the delayed allergic reaction that can occur 3 to 12 days after administering the Infliximab injection product.
Drug History:
The doctor should be provided with a list of prescribed or non-prescribed drugs that the patient is taking, including vitamins and natural or herbal supplements. The patients must inform the doctor if they are taking the following drugs:
-
Anticoagulants or blood thinners such as Warfarin.
-
Antidepressants such as Desipramine, Clomipramine, and Imipramine.
-
Decongestants (medicines for cough and cold).
-
Medications to treat ulcers or heartburn include Esomeprazole, Famotidine, Omeprazole, or Pantoprazole.
-
Medications for high blood pressure.
-
Medications for seizures like Phenytoin, Phenobarbital, and Primidone.
-
Methyldopa.
-
Selective serotonin reuptake inhibitors (SSRIs) include Fluoxetine, Citalopram, Escitalopram, Paroxetine, Fluvoxamine, and Sertraline.
-
Sodium bicarbonate.
-
Venlafaxine.
The patients must inform the doctor if they are taking monoamine oxidase (MAO) inhibitors such as
-
Isocarboxazid.
-
Linezolid.
-
Methylene blue.
-
Phenelzine
-
Rasagiline.
-
Selegiline.
-
Tranylcypromine.
The patient should inform the doctor if these drugs are discontinued during the past 14 days, as the doctor may not prescribe Methylphenidate hydrochloride until 14 days have passed since the administration of an MAO inhibitor.
The doctor should also be informed if the patient is taking Ritalin LA, antacids, or other medications for heartburn or ulcers. The doctor might have to monitor the side effects carefully or change the dose.
Medical History:
The patient must inform the doctor about the following conditions:
-
Tourette's syndrome (a disorder characterized by repeated motions or a habit of repeating sounds or words).
-
Verbal tics (repetition of sounds that is hard to control).
-
Facial or motor tics (uncontrollable repetitive movements).
-
An overactive thyroid gland.
-
Glaucoma (increased pressure within the eye that might lead to vision loss).
-
Feelings of anxiety or agitation.
-
History of heart attack, high blood pressure, irregular heartbeat, cardiomyopathy (thickening of the heart muscle), or other heart problems.
-
Family history of bipolar disorder (mood ranging from depressed to abnormally excited), depression, mania (frenzied, abnormally excited mood), or other psychological disorders.
Pregnancy and Breastfeeding:
The patients must inform the doctor if they are pregnant or planning to get pregnant. Before prescribing this medication while breastfeeding, the potential risks and benefits must be calculated. The doctor might closely check the baby for unusual behavior like difficulty sleeping, agitation, poor appetite, or weight loss.
Pediatric:
No studies to date have suggested pediatric-specific problems that would limit the usefulness of Methylphenidate hydrochloride in children six years and older. The safety and efficacy of this medication have not been demonstrated in children below six years.
Geriatric:
The risks and benefits of taking Methylphenidate hydrochloride must be calculated in patients 65 years or older. Older patients should avoid taking Methylphenidate hydrochloride because it is not considered safe as other drugs used to treat the same disorder.
Alcoholics:
The patient must avoid the consumption of alcoholic beverages alcoholic while taking the long-acting orally disintegrating tablet, long-acting chewable tablet, or the long-acting capsule.
Phenylketonuria:
Suppose the patient has phenylketonuria (an inherited disorder requiring a special diet to prevent brain damage leading to intellectual disability). In that case, they must be aware that the immediate-release and long-acting chewable tablets can form phenylalanine as it contains aspartame.
What Should Be Done in Case of a Missed Dose?
The missed dose must be taken as soon as the patient remembers it. However, if it is almost time to take the next dose, the missed dose must not be taken, and the regular schedule should be continued. A double dose must not be administered to compensate for the missed dose.
Side Effects:
Methylphenidate hydrochloride can cause various side effects. The doctor must be informed in case of the following symptoms.
-
Nervousness.
-
Irritability.
-
Difficulty falling asleep or staying asleep.
-
Dizziness.
-
Loss of appetite.
-
Nausea.
-
Vomiting.
-
Weight loss.
-
Heavy sweating.
-
Back pain.
-
Restlessness.
-
Stomach pain.
-
Muscle tightness.
-
Heartburn.
-
Dry mouth.
-
Headache.
-
Drowsiness.
-
Uncontrolled body movement.
-
Decreased libido.
Sometimes these side effects can be severe and need immediate attention.
-
Fast, pounding, or irregular heartbeat.
-
Chest pain.
-
Shortness of breath.
-
Difficulty swallowing.
-
Excessive tiredness.
-
Changes in vision or blurred vision.
-
Agitation.
-
Difficulty in speech.
-
Fainting.
-
Weakness or numbness of an arm.
-
Believing in things that are not true.
-
Seizures.
-
Feeling unusually suspicious of others.
-
Hallucinating (visualizing things or hearing voices that do not exist).
-
Motor tics or verbal tics.
-
Mood changes.
-
Depression.
-
Abnormally excited mood.
-
Frequent, painful erections.
-
Erection that lasts longer than four hours.
-
Hives.
-
Rash.
-
Blistering or peeling skin.
-
Numbness, sensitivity, or pain to temperature in the extremities.
-
Skin color changes from pale to blue on the fingers or toes.
-
Unexplained wounds on the fingers or toes.
-
Fever.
-
Itching.
-
Swelling of the face, lips, eyes, mouth, tongue, or throat.
-
Hoarseness
The doctor has to monitor the child’s growth as Methylphenidate hydrochloride may lead to slow growth or weight gain in children.
How Should Methylphenidate Hydrochloride Be Stored?
-
The container of this medication should be tightly closed and kept out of reach of children.
-
It must be stored at room temperature and away from light.
-
Methylphenidate hydrochloride should be stored at room temperature and not exposed to excessive moisture and heat.
-
If Methylphenidate hydrochloride is no longer required, it should be disposed of properly so that pets and children do not consume the medications by mistake.
In case of overdose, the poison control helpline must be informed. The symptoms of overdose include the following:
-
Vomiting.
-
Nausea.
-
Diarrhea.
-
Abnormally rapid breathing.
-
Fainting, blurred vision, or dizziness.
-
Restlessness.
-
Agitation.
-
Dry mouth or nose.
-
Muscle twitching.
-
Seizures.
-
Muscle weakness, fatigue, or dark urine.
-
Uncontrolled shaking of a body part.
-
Loss of consciousness.
-
Inappropriate happiness.
-
Confusion.
-
Fast, pounding, or irregular heartbeat.
-
Hallucinating (visualizing things or hearing voices that do not exist).
-
Sweating.
-
Flushing.
-
Headache.
-
Fever.
-
Widening of pupils or black circles in the middle of the eyes.
Other Important Information:
-
Patients taking Methylphenidate hydrochloride long-acting tablets may see something that looks like a tablet in their stool. It is the empty tablet shell, and it does not indicate that the full dose of medication still needs to be received.
-
The doctor usually monitors blood pressure, heart rate, and other lab tests to check the response to Methylphenidate hydrochloride.
-
Maintaining a written list of all the prescribed and non-prescribed (over-the-counter) drugs the patient takes, including other supplements like vitamins or minerals. The patient should carry this list for every visit to a doctor or a hospital. It is extremely important in case of emergencies.
For Doctors:
Indications:
FDA-approved indications include:
-
Attention deficit hyperactivity disorder (ADHD) in children and adults.
-
Second-line treatment for narcolepsy in adults.
Non- FDA approved indications (off-label uses) include
-
Treatment for fatigue in patients with cancer.
-
Refractory depression in the geriatric population.
-
Enhancing cognitive performance.
These indications are still being researched and newly adapted into clinical practice.
Administration:
This drug is usually administered differently in different patients. The amount of the drug usually depends on the strength of the medicine. The number of daily doses and the duration between the doses depend on the medicine used for the disorder.
1. Attention Deficit Hyperactivity Disorder (ADHD):
For Short-Acting Oral Dose (Chewable Tablets or Solution):
-
Adults: 20 to 30 milligrams per day administered twice or thrice daily, 30 to 45 minutes before meals. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Six Years and Older: Initially, 5 mg twice daily, administered before breakfast and lunch. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
For Short-Acting Oral Dose (Tablets):
-
Adults: 20 to 30 milligrams are administered twice or thrice daily, 30 to 45 minutes before meals. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Six Years and Older: Initially, 5 mg twice daily, administered before breakfast and lunch. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
For Long-Acting Oral Dose (Extended-Release Capsules):
[Patients who have not taken Methylphenidate hydrochloride in the past]
-
Adults and Children Six Years and Older: Initially, 10 to 25 milligrams once daily, administered in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 100 mg per day in adults and 85 mg in children.
-
Children Younger Than Six Years: The doctor determines the use and dose.
[Patients who are already taking Methylphenidate hydrochloride]:
-
Adults and Children Six to Twelve Years: Initially, 10 to 60 milligrams once daily, administered in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
For Long-Acting Oral Dose (Extended-Release Suspension):
-
Adults and Children Six Years and Older: Initially, 20 milligrams once daily, administered in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
For Long-Acting Oral Dose (Extended-Release Chewable Tablets):
-
Adults and Children Six Years and Older: Initially, 20 milligrams once daily, administered in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
For Long-Acting Oral Dose (Extended-Release Disintegrating Tablets):
-
Adults and Children Six Years and Older: Initially, 17.3 milligrams once daily, administered in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 51.8 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
For Long-Acting Oral Dose (Extended-Release Tablets):
[For patients who have not been treated with Methylphenidate hydrochloride]
-
Adults: Initially, 18 to 36 milligrams once daily in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 72 mg per day.
-
Teenagers 13 to 17 Years: Initially, 18 milligrams once daily in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 72 mg per day.
-
Children 6 to 12 Years: Initially, 18 milligrams once daily in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 72 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
[For patients already using Methylphenidate hydrochloride]
-
Adults and Children Six Years and Older: Initially, 18 to 72 milligrams once daily, administered in the morning. The doctor can adjust the dose, but not the dose is usually not increased by more than 72 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
2. Narcolepsy:
For Short-Acting Oral Dose (Chewable Tablets or Solution):
-
Adults: 20 to 30 milligrams per day administered twice or thrice daily, 30 to 45 minutes before meals. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Six Years and Older: Initially, 5 mg twice daily, administered before breakfast and lunch. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
For Short-Acting Oral Dose (Tablets):
-
Adults: 20 to 30 milligrams per day administered twice or thrice daily, 30 to 45 minutes before meals. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Six Years and Older: Initially, 5 mg twice daily, administered before breakfast and lunch. The doctor can adjust the dose, but not the dose is usually not increased by more than 60 mg per day.
-
Children Younger Than Six Years: The doctor determines the use and dose.
Precautions:
The patient must inform the doctor if this medication has been taken for a long duration and the patient has become dependent on it. The symptoms of dependency include:
-
An urge to increase the dosage.
-
A strong desire to continue using the medicine.
-
After stopping the medicine, withdrawal symptoms include anxiety, irritability, unusual tiredness or weakness, trouble sleeping or oversleeping, nightmares, increased appetite, agitation, or slowing of mental and physical activity.
Mechanism of Action:
Methylphenidate hydrochloride acts by blocking the reuptake of the following two neurotransmitters in presynaptic neurons:
-
Norepinephrine.
-
Dopamine.
More precisely, it stops the transporters of these neurotransmitters and increases the concentration of norepinephrine or dopamine in the synaptic cleft creating a stimulant effect within the central nervous system (CNS). It is chemically derived from phenethylamine and benzylpiperazine. Compared to other medications derived from phenethylamine, Methylphenidate hydrochloride causes an increase in the firing rate of neurons. Methylphenidate can provide neuroprotection in certain conditions with an increase in dopamine levels, like Parkinson's disease. Methylphenidate acts on both transporters to decrease the amount of dopamine that accumulates within the cytoplasm in patients with these disorders and prevent the formation of reactive oxygen that is otherwise extremely toxic to the brain.
Pharmacokinetics:
Absorption: Extensive but slow.
Relative bioavailability for extended-release tablets:
-
Children: 105 %.
-
Adults: 101 %.
Absolute oral bioavailability for extended-release capsules:
-
Children: 22 % and 5 % for d-methylphenidate and l-methylphenidate, respectively.
Time of Peak Plasma Concentration:
-
Immediate-release tablets: 1.9 hours.
-
Extended-release tablets: 4.7 hours.
Distribution: 2.65 and 1.80 L/kg for d-methylphenidate and l-methylphenidate, respectively.
Plasma Protein Binding: 10 % to 33 %.
Metabolism: Primarily metabolized by de-esterification to ritalinic acid (pharmacologically inactive).
Excretion: 78 % to 97 % is excreted in the urine, and a small amount is excreted in feces.
Administration of This Drug to a Specific Population
-
Patient with Renal Impairment: No dose adjustment is required in the manufacturer label for patients with renal impairment. The drug, with its metabolites, is mostly excreted in the urine.
-
Patient with Hepatic Impairment: No dose adjustment is required in the manufacturer label for patients with renal impairment.
-
Pregnant Women: It is regarded as a pregnancy category C drug. Various studies have been conducted on Methylphenidate hydrochloride during pregnancy for treating ADHD and narcolepsy, but there is a conflict in the data. Therefore, the medication is used with caution during pregnancy.
-
Breastfeeding Women: The infant dose should be kept below 10 % and monitored closely while using Methylphenidate hydrochloride therapy in nursing mothers as the drug is found in breast milk.
-
Pediatric Patients: Various dosage forms and strengths are available for patients aged 6 to 17.
-
Geriatric Patients: No dose adjustment by the manufacturer label is required.
Adverse Effects
The adverse effects of this drug include
-
Insomnia and nervousness.
-
Growth retardation (decreased weight, height, and bone marrow density) if the medication is administered for a long duration in children.
-
Dermatologically, excessive sweating and ulceration of digits may be seen in patients.
-
Blurry vision.
-
Priapism.
Contraindications:
Methylphenidate hydrochloride can not be used if they take monoamine oxidase inhibitors (MAOIs). At least 14 days must elapse before discontinuing MAOIs before administration of Methylphenidate HCl.
Medical conditions where this medication is contraindicated are
-
Glaucoma.
-
Severe hypertension.
-
Motor tics.
Monitoring:
-
The main vitals, like blood pressure and heart rate, must be monitored, particularly in patients with underlying hypertension, heart failure, or ventricular arrhythmia. In addition, a full cardiac workup should be performed if a patient complains of cardiac symptoms, such as chest pain.
-
Methylphenidate hydrochloride can cause dependency hence the signs of dependence must be monitored carefully while the patient is in therapy.
-
A complete blood test must be performed regularly in patients taking Methylphenidate hydrochloride.
-
In adults, patients should limit the consumption of alcohol while taking Methylphenidate hydrochloride as the stimulant action can be ignored by the sedative effect of alcohol intoxication causing severe respiratory depression.
-
Children's growth must be monitored closely to check for any growth retardation.
-
A physical exam must be performed to monitor peripheral vasculitis or digital ulceration.
Drug Interactions:
Using the drug with any of the following medicines is not recommended. The doctor may decide not to administer this medication or change other medicines.
-
Furazolidone.
-
Iproniazid.
-
Isocarboxazid.
-
Linezolid.
-
Methylene Blue.
-
Moclobemide.
-
Nialamide.
-
Phenelzine.
-
Procarbazine.
-
Rasagiline.
-
Safinamide.
-
Selegiline.
-
Tranylcypromine.
Methylphenidate hydrochloride is usually not recommended with any of the following medicines but is sometimes required. If both medicines have to be prescribed together, the doctor may alter the dose or frequency of this medication.
-
Amifampridine.
-
Bupropion.
-
Desflurane.
-
Iobenguane.
-
Donepezil.
-
Risperidone.
-
Sevoflurane.
-
Enflurane.
-
Halothane.
-
Isoflurane.
-
Carbamazepine.
Other Interactions:
Some medicines must not be administered at or around the time of eating. The use of alcohol or tobacco with certain medicines should also be avoided as it might cause interactions.
Involvement of the Healthcare Team:
A proper history must be recorded from the patient or the patient’s legal guardian, which involves a past medical history, social history, and current medications. To provide the best healthcare facilities, an interprofessional team approach must properly diagnose, manage and treat patients with mental disorders. The interprofessional team approach includes clinicians, nurses, mid-level practitioners, therapists, pharmacists, and patients. This team helps the patients understand their illness and encourages them to take the treatment.
