CONCERTA 36MG

Indications

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Dosage

Children: Refer to the BNF for Children for specific

Adults: Refer to the BNF for specific dosing recommendations for adults, as dosages may vary based on individual response and formulation used.

Mechanism of action

Methylphenidate acts as a norepinephrine and dopamine reuptake inhibitor (NDRI), increasing the presence of these neurotransmitters in the extraneuronal space. It selectively enhances norepinephrine and dopamine neurotransmission in the prefrontal cortex at lower doses, which is crucial for improving attention and cognitive function in ADHD. Higher doses may increase locomotor activity and impair cognition, indicating a dose-related effect on receptor stimulation. Its mechanism may also involve modulation of alpha-1 adrenergic receptor activity, which contributes to its efficacy in sustaining attention.

Pharmacodynamics

Methylphenidate is a racemic mixture consisting of d- and l-isomers, with the d-isomer being more pharmacologically active. It selectively binds to dopamine-rich areas in the brain, particularly in the prefrontal cortex, enhancing neurotransmission associated with attention and impulse control. Studies have shown that in animal models, methylphenidate can enhance locomotor activity and induce stereotypic behaviors, which reflects its stimulant properties.

Pharmacokinetics

Methylphenidate is well absorbed after oral administration, with peak plasma concentrations typically occurring within 1 to 2 hours for immediate-release formulations. The drug undergoes extensive hepatic metabolism, primarily via the cytochrome P450 system, with a biological half-life ranging from 2 to 4 hours, depending on the formulation. The drug is excreted mainly in the urine as metabolites, with minimal unchanged drug detected. Variability in metabolism can occur due to genetic factors and concurrent medications.

Contra-indications

• Hypersensitivity to methylphenidate or any of its components
• Glaucoma
• Severe anxiety, tension or agitation
• History of substance use disorder
• Severe hypertension
• Cardiovascular disorders

Adverse effects

• Insomnia
• Decreased appetite
• Abdominal pain
• Nausea
• Headache
• Increased heart rate
• Hypertension
• Mood swings
• Tics

Interactions

• methylphenidate + apraclonidine: Severe (decreases effects)
• methylphenidate + linezolid: Severe (increases risk of elevated blood pressure)
• methylphenidate + rasagiline: Severe (increases risk of a hypertensive crisis)
• methylphenidate + MAO inhibitors: Severe (increases risk of a hypertensive crisis)
• methylphenidate + tricyclic antidepressants: Moderate (increases concentration)
• methylphenidate + alcohol: Unknown (increases concentration)
• methylphenidate + carbamazepine: Unknown (decreases concentration)
• methylphenidate + ozanimod: Unknown (increases risk of a hypertensive crisis)
• methylphenidate + volatile halogenated anesthetics: Unknown (increases risk of hypertension and arrhythmias)

Precautions

• Monitor blood pressure and heart rate regularly during treatment
• Use with caution in patients with a history of cardiovascular disorders
• Consider psychiatric evaluation for patients with a history of mental illness
• Avoid abrupt discontinuation to prevent withdrawal symptoms
• Evaluate for potential misuse or dependence

Pregnancy

Methylphenidate should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult healthcare professionals for guidance.

Breast-feeding

Methylphenidate is excreted in breast milk. Use with caution and consider risks versus benefits when prescribing to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Immediate-release tablets

Indications

• Attention deficit hyperactivity disorder (ADHD) in children aged 6 years and older
• ADHD in adolescents
• ADHD in adults

Dosage

Children: For children aged 6-17 years, the initial dose is 5 mg taken 1-2 times daily, which can be increased by 5-10 mg daily at weekly intervals, up to a maximum of 60 mg per day in 2-3 divided doses. Refer to the BNF for Children for specific dosing guidelines.

Adults: The initial dose for adults is typically 10 mg taken once or twice daily, which may be increased weekly in increments of 5-10 mg as needed, with a maximum dose of 60 mg per day in divided doses.

Mechanism of action

Methylphenidate hydrochloride works by inhibiting the reuptake of norepinephrine and dopamine in the brain, increasing their concentrations in the synaptic cleft. This action enhances neurotransmission associated with attention and behavior regulation, contributing to improved focus and decreased impulsivity.

Pharmacodynamics

Methylphenidate exhibits stimulant properties that enhance cognitive function, particularly in attention and behavior. The therapeutic effects are observed in improved concentration, reduced hyperactivity, and better impulse control. These effects are dose-dependent and can vary among individuals.

Pharmacokinetics

Methylphenidate is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It is metabolized predominantly in the liver and has a half-life ranging from 2 to 4 hours. The drug is excreted mainly in the urine as metabolites, with minimal unchanged drug found in the urine. Its pharmacokinetic profile may vary based on the formulation used (immediate-release vs. extended-release).

Contra-indications

• Known hypersensitivity to methylphenidate or any of its components
• Severe anxiety, tension, or agitation
• Glaucoma
• Tic disorders, including Tourette's syndrome
• Severe cardiovascular disorders
• Hyperthyroidism
• History of drug abuse

Adverse effects

• Insomnia
• Decreased appetite
• Nausea
• Vomiting
• Headache
• Irritability
• Increased heart rate
• Hypertension
• Anxiety
• Mood changes, including depression or aggression

Interactions

• May interact with monoamine oxidase inhibitors (MAOIs), leading to hypertensive crisis
• Increased risk of serotonin syndrome when used with other serotonergic agents
• May reduce the effectiveness of antihypertensive drugs
• Caution with other stimulants or sympathomimetics

Precautions

• Monitor blood pressure and heart rate periodically
• Evaluate for the potential for abuse and dependence
• Consider potential exacerbation of psychiatric disorders
• Use with caution in patients with a history of substance use disorders
• Regularly assess growth in children

Pregnancy

Manufacturer advises avoid unless potential benefit outweighs risk.

Breast-feeding

Avoid; present in milk in animal studies.

Storage

Store in a cool, dry place away from light, and keep out of reach of children.

Formulations

• Methylphenidate hydrochloride 5 mg tablets
• Methylphenidate hydrochloride 10 mg tablets
• Methylphenidate hydrochloride 20 mg tablets
• Methylphenidate hydrochloride 18 mg extended-release capsules
• Methylphenidate hydrochloride 27 mg extended-release capsules
• Methylphenidate hydrochloride 36 mg extended-release capsules
• Methylphenidate hydrochloride 54 mg extended-release capsules

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. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Although the primary mechanism is largely unknown, the effects of methylphenidate appear to be mediated by blockage of the reuptake mechanism of dopaminergic neurons. In children with attention deficit disorder, methylphenidate decreases motor restlessness and enhances the ability to pay attention. In narcolepsy, methylphenidate appears to act at the cerebral cortex and subcortical structures, including the thalamus, to produce CNS stimulation, resulting in increaed motor activity, increased mental alertness, diminished sense of fatigue, brighter spirits, and mild euphoria. Mode of action: Appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especially norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase.

Pharmacodynamics

Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer. Radioligand binding studies demonstrate that binding of methylphenidate in the brain is localized to dopamine-rich areas, in particular in the prefrontal cortex which has been demonstrated to play a prominent role in ADHD pathophysiology. In a number of animal models, methylphenidate enhances locomotor activity and induces stereotypic behaviours.