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EQUASYM 20MG TABLETS

Active substance(s): METHYLPHENIDATE HYDROCHLORIDE / METHYLPHENIDATE HYDROCHLORIDE / METHYLPHENIDATE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
EQUASYM™ 20MG TABLETS

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Methylphenidate Hydrochloride 20mg

3

PHARMACEUTICAL FORM
Tablet with breakline, “Medeva” and strength embossed on one side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Methylphenidate is indicated as part of a comprehensive treatment programme for attentiondeficit/hyperactivity disorder (ADHD) in children aged 6 years of age and over when
remedial measures alone prove insufficient. Treatment must be under the supervision of a
specialist in childhood behavioural disorders. Diagnosis should be made according to DSMIV criteria or the guidelines in ICD-10 and should be based on a complete history or
evaluation of the patient. Diagnosis cannot be made solely on the presence of one or more
symptom.
The specific aetiology of this syndrome is unknown, and there is no single diagnostic test.
Adequate diagnosis requires the use of medical and specialised psychological, educational,
and social resources.
A comprehensive treatment programme typically includes psychological, educational and
social measures as well as pharmacotherapy and is aimed at stabilising children with a
behavioural syndrome characterised by symptoms which may include chronic history of short
attention span, distractibility, emotional lability, impulsivity, moderate to severe
hyperactivity, minor neurological signs and abnormal EEG. Learning may or may not be
impaired.

Methylphenidate treatment is not indicated in all children with this syndrome and the decision
to use the drug must be based on a very thorough assessment of the severity and chronicity of
the child’s symptoms in relation to the child’s age.
Appropriate educational placement is essential, and psychosocial intervention is generally
necessary. Where remedial measures alone prove insufficient, the decision to prescribe a
stimulant must be based on rigorous assessment of the severity of the child's symptoms. The
use of methylphenidate should always be used in this way according to the licensed indication
and according to prescribing / diagnostic guidelines.

4.2

Posology and method of administration

Children: (aged 6 years and over) and adolescents:
Treatment must be initiated under the supervision of a specialist in childhood and/or
adolescent behavioural disorders.
Pre-treatment screening:
Prior to prescribing, it is necessary to conduct a baseline evaluation of a patient’s
cardiovascular status including blood pressure and heart rate. A comprehensive history should
document concomitant medications, past and present co-morbid medical and psychiatric
disorders or symptoms, family history of sudden cardiac/unexplained death and accurate
recording of pre-treatment height and weight on a growth chart (see sections 4.3 and 4.4).
Ongoing monitoring:
Growth, psychiatric and cardiovascular status should be continuously monitored (see also
Section 4.4).




Blood pressure and pulse should be recorded on a centile chart at each adjustment of dose
and then at least every 6 months;
height, weight and appetite should be recorded at least 6 monthly with maintenance of a
growth chart;
development of de novo or worsening of pre-existing psychiatric disorders should be
monitored at every adjustment of dose and then least every 6 months and at every visit.

Patients should be monitored for the risk of diversion, misuse and abuse of methylphenidate.
Dose titration:
Careful dose titration is necessary at the start of treatment with methylphenidate. Dose
titration should be started at the lowest possible dose. The recommended starting daily dose is
5 mg once daily or twice daily (e.g. at breakfast and lunch), increasing if necessary by weekly
increments of 5-10 mg in the daily dose according to tolerability and degree of efficacy
observed.
The maximum daily dose of methylphenidate hydrochloride is 60 mg. The total daily dose
should be administered in divided doses.
For doses not realisable/practicable with this strength, other strengths of this medicinal
product and other methylphenidate containing products are available.

The last doses should, in general, not be given within 4 hours before bedtime in order to
prevent disturbances in falling asleep. However, if the effect of the drug wears off too early in
the evening, disturbed behaviour and/or inability to go to sleep may recur. A small evening
dose may help to solve this problem. The pros and cons of a small evening dose versus
disturbances in falling asleep should be considered.
Long-term (more than 12 months) use in children and adolescents:
The safety and efficacy of long term use of methylphenidate has not been systematically
evaluated in controlled trials. Methylphenidate treatment should not and need not, be
indefinite. Methylphenidate treatment is usually discontinued during or after puberty. The
physician who elects to use methylphenidate for extended periods (over 12 months) in
children and adolescents with ADHD should periodically re-evaluate the long term usefulness
of the drug for the individual patient with trial periods off medication to assess the patient’s
functioning without pharmacotherapy. It is recommended that methylphenidate is dechallenged at least once yearly to assess the child’s condition (preferable during times of
school holidays). Improvement may be sustained when the drug is either temporarily or
permanently discontinued.
Dose reduction and discontinuation
Treatment must be stopped if the symptoms do not improve after appropriate dosage
adjustment over a one-month period. If paradoxical aggravation of symptoms or other serious
adverse events occur, the dosage should be reduced or discontinued.
Adults
Methylphenidate is not licensed for use in adults in ADHD. Safety and efficacy have not been
established in this age group.
Elderly
Methylphenidate should not be used in the elderly. Safety and efficacy has not been
established in this age group.
Children under 6 years of age
Methylphenidate should not be used in children under the age of 6 years. Safety and efficacy
in this age group has not been established.

4.3

Contraindications

Equasym is contra-indicated in patients with:








Known sensitivity to methylphenidate or to any of the excipients
Glaucoma
Phaeochromocytoma
During treatment with non-selective, irreversible monoamine oxidase inhibitors, or
within a minimum of 14 days following discontinuing those drugs, due to risk of
hypertensive crises (see Section 4.5)
Hyperthyroidism or Thyrotoxicosis
Diagnosis or history of severe depression, anorexia nervosa/anorexic disorders suicidal
tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia,
psychopathic/borderline personality disorder
Diagnosis or history of severe and episodic (Type I) Bipolar (affective) disorder (that is
not well-controlled)





4.4

Pre-existing cardiovascular disorders including severe hypertension, heart failure,
arterial occlusive disease, haemodynamically significant congenital heart disease,
cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and
channelopathies (disorders caused by the dysfunction of ion channels)
Pre-existing cerebrovascular disorders cerebral aneurysm, vascular abnormalities
including vasculitis or stroke

Special warnings and precautions for use

Methylphenidate treatment is not indicated in all children with ADHD and the decision to use
the drug must be based on a very thorough assessment of the severity and chronicity of the
child’s symptoms in relation to the child’s age.
Long-term use (more than 12 months) in children and adolescents
The safety and efficacy of long term use of methylphenidate has not been systematically
evaluated in controlled trials. Methylphenidate treatment should not and need not, be
indefinite. Methylphenidate treatment is usually discontinued during or after puberty.
Patients on long-term therapy (i.e. over 12 months) must have careful ongoing monitoring
according to the guidance in sections 4.2 and 4.4. for cardiovascular status, growth, appetite,
development of de novo or worsening of pre-existing psychiatric disorders. Psychiatric
disorders to monitor for are described below, and include (but are not limited to) motor or
vocal tics, aggressive or hostile behaviour, agitation, anxiety, depression, psychosis, mania,
delusions, irritability, lack of spontaneity, withdrawal and excessive perseveration.
The physician who elects to use methylphenidate for extended periods (over 12 months) in
children and adolescents with ADHD should periodically re-evaluate the long term usefulness
of the drug for the individual patient with trial periods off medication to assess the patient’s
functioning without pharmacotherapy. It is recommended that methylphenidate is dechallenged at least once yearly to assess the child’s condition (preferably during times of
school holidays). Improvement may be sustained when the drug is either temporarily or
permanently discontinued.
Use in adults
Methylphenidate is not licensed for use in adults with ADHD. Safety and efficacy have not
been established in this age group.
Use in the elderly
Methylphenidate should not be used in the elderly. Safety and efficacy has not been
established in this age group.
Use in children under 6 years of age
Methylphenidate should not be used in children under the age of 6 years. Safety and efficacy
in this age group has not been established.
Cardiovascular status
Patients who are being considered for treatment with stimulant medications should have a
careful history (including assessment for a family history of sudden cardiac or unexplained
death or malignant arrhythmia) and physical exam to assess for the presence of cardiac
disease, and should receive further specialist cardiac evaluation if initial findings suggest such
history or disease. Patients who develop symptoms such as palpitations, exertional chest pain,

unexplained syncope, dyspnoea or other symptoms suggestive of cardiac disease during
methylphenidate treatment should undergo a prompt specialist cardiac evaluation.
Analyses of data from clinical trials of methylphenidate in children and adolescents with
ADHD showed that patients using methylphenidate may commonly experience changes in
diastolic and systolic blood pressure of over 10 mmHg relative to controls. The short- and
long-term clinical consequences of these cardiovascular effects in children and adolescents
are not known, but the possibility of clinical complications cannot be excluded as a result of
the effects observed in the clinical trial data. Caution is indicated in treating patients whose
underlying medical conditions might be compromised by increases in blood pressure or
heart rate. See section 4.3 for conditions in which methylphenidate treatment in
contraindicated.
Cardiovascular status should be carefully monitored. Blood pressure and pulse should
be recorded on a centile chart at each adjustment of dose and then at least every 6
months.
The use of methylphenidate is contraindicated in certain pre-existing cardiovascular disorders
unless specialist paediatric cardiac advice has been obtained (see Section 4.3
‘Contraindications’).
Sudden death and pre-existing cardiac structural abnormalities or other serious cardiac
disorders
Sudden death has been reported in association with the use of stimulants of the central
nervous system at usual doses in children, some of whom had cardiac structural abnormalities
or other serious heart problems. Although some serious heart problems alone may carry an
increased risk of sudden death, stimulant products are not recommended in children or
adolescents with known cardiac structural abnormalities, cardiomyopathy, serious heart
rhythm abnormalities, or other serious cardiac problems that may place them at increased
vulnerability to the sympathomimetic effects of a stimulant medicine.
Misuse and Cardiovascular Events
Misuse of stimulants of the central nervous system may be associated with sudden death and
other serious cardiovascular adverse events.
Cerebrovascular disorders
See section 4.3 for cerebrovascular conditions in which methylphenidate treatment in
contraindicated. Patients with additional risk factors (such as a history of cardiovascular
disease, concomitant medications that elevate blood pressure) should be assessed at every
visit for neurological signs and symptoms after initiating treatment with methylphenidate.
Cerebral vasculitis appears to be a very rare idiosyncratic reaction to methylphenidate
exposure. There is little evidence to suggest that patients at higher risk can be identified and
the initial onset of symptoms may be the first indication of an underlying clinical problem.
Early diagnosis, based on a high index of suspicion, may allow the prompt withdrawal of
methylphenidate and early treatment. The diagnosis should therefore be considered in any
patient who develops new neurological symptoms that are consistent with cerebral ischemia
during methylphenidate therapy. These symptoms could include severe headache, numbness,
weakness, paralysis, and impairment of coordination, vision, speech, language or memory.
Treatment with methylphenidate is not contraindicated in patients with hemiplegic cerebral
palsy.

Psychiatric disorders
Co-morbidity of psychiatric disorders in ADHD is common and should be taken into account
when prescribing stimulant products. In the case of emergent psychiatric symptoms or
exacerbation of pre-existing psychiatric disorders, methylphenidate should not be given
unless the benefits outweigh the risks to the patient.
Development or worsening of psychiatric disorders should be monitored at every
adjustment of dose, then at least every 6 months, and at every visit; discontinuation of
treatment may be appropriate.
Exacerbation of pre-existing Psychotic or manic symptoms
In psychotic patients, administration of methylphenidate may exacerbate symptoms of
behavioural disturbance and thought disorder.
Emergence of new psychotic or manic symptoms
Treatment-emergent psychotic symptoms (visual/tactile/auditory hallucinations and
delusions) or mania in children and adolescents without prior history of psychotic illness or
mania can be caused by methylphenidate at usual doses. If manic or psychotic symptoms
occur, consideration should be given to a possible causal role for methylphenidate, and
discontinuation of treatment may be appropriate.
Aggressive or hostile behaviour
The emergence or worsening of aggression or hostility can be caused by treatment with
stimulants. Patients treated with methylphenidate should be closely monitored for the
emergence or worsening of aggressive behaviour or hostility at treatment initiation, at every
dose adjustment and then at least every 6 months and every visit. Physicians should evaluate
the need for adjustment of the treatment regimen in patients experiencing behaviour changes.
Suicidal tendency
Patients with emergent suicidal ideation or behaviour during treatment for ADHD should be
evaluated immediately by their physician. Consideration should be given to the exacerbation
of an underlying psychiatric condition and to a possible causal role of methylphenidate
treatment. Treatment of an underlying psychiatric condition may be necessary and
consideration should be given to a possible discontinuation of methylphenidate.
Tics
Methylphenidate is associated with the onset or exacerbation of motor and verbal tics.
Worsening of Tourette’s syndrome has also been reported. Family history should be assessed
and clinical evaluation for tics or Tourette’s syndrome in children should precede use of
methylphenidate. Patients should be regularly monitored for the emergence or worsening of
tics during treatment with methylphenidate. Monitoring should be at every adjustment of
dose and then at least every 6 months or every visit.
Anxiety, agitation or tension
Methylphenidate is associated with the worsening of pre-existing anxiety, agitation or tension.
Clinical evaluation for anxiety, agitation or tension should precede use of methylphenidate
and patients should be regularly monitored for the emergence or worsening of these
symptoms during treatment, at every adjustment of dose and then at least every 6
month or every visit.
Forms of bipolar disorder
Particular care should be taken in using methylphenidate to treat ADHD in patients with
comorbid bipolar disorder (including untreated Type I Bipolar Disorder or other forms of

bipolar disorder) because of concern for possible precipitation of a mixed/manic episode in
such patients. Prior to initiating treatment with methylphenidate, patients with comorbid
depressive symptoms should be adequately screened to determine if they are at risk for
bipolar disorder; such screening should include a detailed psychiatric history, including a
family history of suicide, bipolar disorder, and depression. Close ongoing monitoring is
essential in these patients (see above ‘Psychiatric Disorders’ and section 4.2). Patients
should be monitored for symptoms at every adjustment of dose, then at least every 6
months and at every visit.
Growth
Moderately reduced weight gain and growth retardation have been reported with the longterm use of methylphenidate in children.
The effects of methylphenidate on final height and final weight are currently unknown and
being studied.
Growth should be monitored during methylphenidate treatment: height, weight and
appetite should be recorded at least 6 monthly with maintenance of a growth chart.
Patients who are not growing or gaining height or weight as expected may need to have their
treatment interrupted.
Seizures
Methylphenidate should be used with caution in patients with epilepsy. Methylphenidate may
lower the convulsive threshold in patient with prior history of seizures, in patients with prior
EEG abnormalities in absence of seizures, and rarely in patients without a history of
convulsions and no EEG abnormalities. If seizure frequency increases or new-onset seizures
occur, methylphenidate should be discontinued.
Abuse, misuse and diversion
Patients should be carefully monitored for the risk of diversion, misuse and abuse of
methylphenidate.
Methylphenidate should be used with caution in patients with known drug or alcohol
dependency because of a potential for abuse, misuse or diversion.
Chronic abuse of methylphenidate can lead to marked tolerance and psychological
dependence with varying degrees of abnormal behaviour. Frank psychotic episodes can occur,
especially in response to parenteral abuse.
Patient age, the presence of risk factors for substance use disorder (such as co-morbid
oppositional-defiant or conduct disorder and bipolar disorder), previous or current substance
abuse should all be taken into account when deciding on a course of treatment for ADHD.
Caution is called for in emotionally unstable patients, such as those with a history of drug or
alcohol dependence, because such patients may increase the dosage on their own initiative.
For some high-risk substance abuse patients, methylphenidate or other stimulants may not be
suitable and non-stimulant treatment should be considered.
Withdrawal
Careful supervision is required during drug withdrawal, since this may unmask depression as
well as chronic over-activity. Some patients may require long-term follow up.

Careful supervision is required during withdrawal from abusive use since severe depression
may occur.
Fatigue
Methylphenidate should not be used for the prevention or treatment of normal fatigue states.
Excipients: galactose intolerance
This medicinal product contains lactose: patients with rare hereditary problems of galactose
intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this
medicine.
Choice of methylphenidate formulation
The choice of formulation of methylphenidate-containing product will have to be decided by
the treating specialist on an individual basis and depends on the intended duration of effect.
Drug screening
This product contains methylphenidate which may induce a false positive laboratory test for
amphetamines, particularly with immunoassay screen test.
Renal or hepatic insufficiency
There is no experience with the use of methylphenidate in patients with renal or hepatic
insufficiency.
Haematological effects
The long-term safety of treatment with methylphenidate is not fully known. In the event of
Leukopenia, thrombocytopenia, anaemia or other alterations, including those indicative of
serious renal or hepatic disorders, discontinuation of treatment should be considered.

4.5

Interaction with other medicinal products and other forms of interaction

Pharmacokinetic interaction
It is not known how methylphenidate may affect plasma concentrations of concomitantly
administered drugs. Therefore, caution is recommended at combining methylphenidate with
other drugs, especially those with a narrow therapeutic window.
Methylphenidate is not metabolised by cytochrome P450 to a clinically relevant extent.
Inducers or inhibitors of cytochrome P450 are not expected to have any relevant impact on
methylphenidate pharmacokinetics. Conversely, the d- and l- enantiomers of methylphenidate
do not relevantly inhibit cytochrome P450 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A.
However, there are reports indicating that methylphenidate may inhibit the metabolism of
coumarin anticoagulants, anticonvulsants (e.g. phenobarbital, phenytoin, primidone) and
some antidepressants (tricyclics and selective serotonin reuptake inhibitors). When starting or
stopping treatment with methylphenidate, it may be necessary to adjust the dosage of these
drugs already being taken and establish drug plasma concentrations (or for coumarin,
coagulation times).
Pharmacodynamic interactions
Anti-hypertensive drugs
Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.

Use with drugs that elevate blood pressure
Caution is advised in patients being treated with methylphenidate with any other drug that can
also elevate blood pressure (see also sections on cardiovascular and cerebrovascular
conditions in Section 4.4 Warnings and Precautions for use).
Because of possible hypertensive crisis, methylphenidate is contraindicated in patients being
treated (currently or within the preceding 2 weeks) with non-selective, irreversible MAOinhibitors (see section 4.3 Contraindications).
Use with alcohol
Alcohol may exacerbate the CNS adverse reactions of psychoactive drugs, including
methylphenidate. It is therefore advisable for patients to abstain from alcohol during
treatment.
Use with halogenated anaesthetics
There is a risk of sudden blood pressure increase during surgery. If surgery is planned,
methylphenidate treatment should not be used on the day of surgery.
Use with centrally acting alpha-2 agonists (e.g. clonidine)
Serious adverse events, including sudden death, have been reported in concomitant use with
clonidine. The safety of using methylphenidate in combination with clonidine or other
centrally acting alpha-2 agonists has not been systematically evaluated.
Use with domapinergic drugs
Caution is recommended when administering methylphenidate with dopaminergic drugs,
including antipsychotics. Because a predominant action of methylphenidate is to increase
extracelluar dopamine levels, methylphenidate may be associated with pharmacodynamic
interactions when co-administered with direct and indirect dopamine agonists (including
DOPA and tricyclic antidepressants) or with dopamine antagonists including antipsychotics.

4.6

Pregnancy and lactation

Pregnancy
There is limited amount of data from the use of methylphenidate in pregnant women.
Cases of neonatal cardiorespiratory toxicity, specifically fetal tachycardia and respiratory
distress have been reported in spontaneous case reports.
Studies in animals have only shown reproductive toxicity at maternally toxic doses (see
Section 5.3).
Methylphenidate is not recommended for use during pregnancy unless a clinical decision is
made that postponing treatment may pose a greater risk to the pregnancy.
Lactation
Methylphenidate has been found in the breast-milk of a woman treated with methylphenidate.
There is one case report of an infant who experienced an unspecified decrease in weight
during the period of exposure but recovered and gained weight after the mother discontinued
treatment with methylphenidate. A risk to the suckling child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from
methylphenidate therapy taking into account the benefit of breast feeding for the child and the
benefit of therapy for the woman.

4.7

Effects on ability to drive and use machines

Methylphenidate may cause dizziness, drowsiness and visual disturbances including
difficulties with accommodations, diplopia and blurred vision. It may have a moderate
influence on the ability to drive and use machines. Patients should be warned of these possible
effects and advised that if affected, they should avoid potentially hazardous activities such as
driving or operating machinery.

4.8

Undesirable effects

The table below shows all adverse drug reactions (ADRs) observed during clinical trials and
post-market spontaneous reports with Equasym and those, which have been reported with
other methylphenidate hydrochloride formulations. If the ADRs with Equasym and the
methylphenidate formulation frequencies were different, the highest frequency of both
databases was used.
Frequency estimate: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥
1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (<1/10000), not known (cannot be
estimated from the available data).

System Organ Class
Adverse Drug Reaction
Infections and infestations
Common:
Nasopharyngitis
Blood and lymphatic system disorders
Very rare:
anaemia, leucopenia, thrombocytopenia,
thrombocytopenic purpura
Unknown:
pancytopenia
Immune System Disorders
Uncommon:
hypersensitivity reactions such as angioneurotic
oedema, anaphylactic reactions, auricular swelling,
bullous conditions, exfoliative conditions, urticarias,
pruritis, rashes and eruptions
Metabolism and nutrition disorders*
Common:
anorexia, decreased appetite, moderately reduced
weight and height gain during prolonged use in
children*
Psychiatric disorders*
Very common:
insomnia, nervousness
Common:
anorexia, affect lability, aggression*, agitation*,
anxiety*, depression*, irritability, abnormal
Uncommon:
behaviour
psychotic disorders*, auditory, visual, and tactile
hallucinations*, anger, suicidal ideation*, mood
altered, mood swings, restlessness, tearfulness, tics*,

worsening of pre-existing tics or Tourette’s
syndrome*, hypervigilance, sleep disorder
mania*, disorientation, libido disorder
suicidal attempt (including completed suicide)*,
transient depressed mood*, abnormal thinking,
Not known:
apathy, repetitive behaviours, over-focussing
delusions*, thought disturbances*, confusional state,
dependence
Cases of abuse and dependence have been described, more often with immediate
release formulations (frequency not known)
Nervous system disorders
Very common:
headache
Common:
dizziness, dyskinesia, psychomotor hyperactivity
Uncommon:
somnolence, sedation, tremor
Very rare:
convulsions, choreo-athetoid movements, reversible
ischaemic neurological deficit Neuroleptic malignant
syndrome (NMS; Reports were poorly documented
and in most cases, patients were also receiving other
drugs, so the role of methylphenidate is unclear)
Not known:
cerebrovascular disorders* (including vasculitis,
cerebral haemorrhages, cerebrovascular accidents,
cerebral arteritis, cerebral occlusion), grand mal
convulsions*, migraine
Eye disorders
Uncommon:
diplopia, blurred vision
Rare:
difficulties in visual accommodation, mydriasis,
visual disturbance
Cardiac disorders
Common:
arrhythmia, tachycardia, palpitations
Uncommon:
chest pain
Rare:
angina pectoris
Very rare:
cardiac arrest, myocardial infarction
Unknown:
supraventricular tachycardia, bradycardia, ventricular
extrasystoles, extrasystoles
Vascular disorders*
Common:
hypertension
Very rare:
cerebral arteritis and/or occlusion, peripheral
coldness, Raynaud’s phenomenon
Respiratory, thoracic and mediastinal disorders
Common:
cough, pharyngolaryngeal pain
Uncommon:
dyspnoea
Gastrointestinal disorders
Common:
abdominal pain, diarrhea, nausea, stomach
discomfort and vomiting, dry mouth
Uncommon:
constipation
Hepatobiliary disorders
Uncommon:
hepatic enzyme elevations
Very rare:
abnormal liver function, including hepatic coma
Skin and subcutaneous tissue disorders
Common:
alopecia, pruritus, rash, urticaria
Uncommon:
angioneurotic oedema, bullous conditions,
exfoliative conditions
Rare:
hyperhidrosis, macular rash, erythema
Rare:
Very rare:

Very rare:

erythema multiforme, exfoliative dermatitis, fixed
drug eruption
Musculoskeletal and connective tissue disorders
Common:
arthralgia
Uncommon:
myalgia, muscle twitching
Very rare:
muscle cramps
Renal and urinary disorders
Uncommon:
Haematuria
Reproductive system and breast disorders
Rare:
Gynaecomastia
General disorders and administration site conditions
Common:
pyrexia, growth retardation during prolonged use in
children*
Uncommon:
chest pain, fatigue
Very rare:
sudden cardiac death*
Unknown:
chest discomfort, hyperpryrexia
Investigations
Common:
changes in blood pressure and heart rate (usually an
increase) *, weight decreased
Uncommon:
cardiac murmur*, hepatic enzyme increased
Very rare:
blood alkaline phosphatase increased, blood bilirubin
increased, platelet count decreased, white blood
count abnormal
*

4.9

See Section 4.4 ‘Special Warnings and precautions for use’

Overdose

Signs and symptoms
Acute overdose, mainly due to overstimulation of the central and sympathetic nervous
systems, may result in vomiting, agitation, tremors, hyperreflexia, muscle twitching,
convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium,
sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias,
hypertension, mydriasis and dryness of mucous membranes.
Treatment
There is no specific antidote to methylphenidate overdosage.
Treatment consists of appropriate supportive measures.
The patient must be protected against self injury and against external stimuli that would
aggravate overstimulation already present. If the signs and symptoms are not too severe and
the patient is conscious, gastric contents may be evacuated by induction of vomiting or gastric
lavage. Before performing gastric lavage, control agitation and seizures if present and protect
the airway. Other measures to detoxify the gut include administration of activated charcoal
and a cathartic. In the presence of severe intoxication, a carefully titrated dose of a
benzodiazepine should be given before performing gastric lavage.
Intensive care must be provided to maintain adequate circulation and respiratory exchange;
external cooling procedures may be required for hyperpyrexia.

Efficacy of peritoneal dialysis or extracorporeal haemodialysis for overdose of
methylphenidate has not been established.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Psychoanaleptics, Psychostimulants and Nootropics, Centrally
acting Sympathomimetics, ATC code: N06B A04.
Mode of action: Methylphenidate is a CNS stimulant. The mode of action is not completely
understood. Methylphenidate is an indirect sympatheticomimetic. The pharmacological
properties are amphetamine-like.
MAO-enzyme inhibition may result in an increased catecholamine concentration.

5.2

Pharmacokinetic properties
Absorption: The active substance methylphenidate hydrochloride is rapidly
and almost completely absorbed from the tablets. Owing to extensive
first-pass metabolism its systemic availability amounts to only 30% (11-51%)
of the dose. Ingestion together with food accelerates its absorption, but has no
influence on the amount absorbed. Peak plasma concentrations of
approximately 40 nmol/litre (11 ng/ml) are attained, on average, 1-2 hours
after administration of 0.30 mg/kg. The peak plasma concentrations, however,
show considerable intersubject variability. The area under the plasma
concentration curve (AUC), as well as the peak plasma concentration, are
proportional to the dose.
Distribution: In the blood, methylphenidate and its metabolites become
distributed in the plasma (57%) and the erythrocytes (43%). Methylphenidate
and its metabolites have a low plasma protein-building rate (10-33%). The
apparent distribution volume has been calculated as 13.1 litres/kg.
Biotransformation: Biotransformation of methylphenidate is rapid and
extensive. Peak plasma concentrations of 2-phenyl -2-piperidyl acetic acid
(PPAA) are attained approximately 2 hours after administration of
methylphenidate and are 30 - 50 times higher than those of the unchanged
substance. The half life of PPAA is roughly twice as long as that of
methylphenidate, and the mean systemic clearance is 0.17 litres/h/kg. Only
small amounts of hydroxylated metabolites (e.g. hydroxymethylphenidate and
hydroxyritalinic acid) are detectable. Therapeutic activity seems to be
principally due to the parent compound.
Elimination: Methylphenidate is eliminated from the plasma with a mean
half-life of 2 hours, and the calculated mean systemic clearance is
10 litres/h/kg. Within 48-96 hours 78-97% of the dose administered is

excreted in the urine and 1-3% in the faeces in the form of metabolites.
Unchanged methylphenidate appears in the urine only in small quantities
(<1%). The bulk of the dose is excreted in the urine as 2-phenyl-2-piperidyl
acetic acid (PPAA, 60-86%).
Characteristics in patients: There are no apparent differences in the
pharmacokinetic behaviour of methylphenidate in hyperactive children and
healthy adult volunteers.
Elimination data from patients with normal renal function suggest that renal
excretion of the unchanged methylphenidate would hardly be diminished at all
in the presence of impaired renal function. However, renal excretion of PPAA
may be reduced.

5.3

Preclinical safety data

Carcinogenicity
In life-time rat and mouse carcinogenicity studies, increased numbers of malignant liver
tumours were noted in male mice only. The significance of this finding to humans is
unknown.
Methylphenidate did not affect reproductive performance or fertility at low multiples of the
clinical dose.
Pregnancy-embryonal/fetal development
Methylphenidate is not considered to be a teratogenic in rats and rabbits. Fetal toxicity (i.e.
total litter loss) and maternal toxicity was noted in rats at maternally toxic doses.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Anhydrous Lactose
Magnesium Stearate
Microcrystalline Cellulose
Sodium Starch Glycollate

6.2

Incompatibilities

None known

6.3.

Shelf life
3 years.

6.4

Special precautions for storage
Do not store above 25°C. Store in the original package.

6.5

Nature and contents of container
Blister packs of 30 tablets.

6.6

Special precautions for disposal
Do not use after the expiry date on the pack. Keep out of the reach of
children.

7

MARKETING AUTHORISATION HOLDER
Shire Pharmaceuticals Ireland Limited
5 Riverwalk
Citywest Business Campus
Dublin 24
Ireland

8

MARKETING AUTHORISATION NUMBER(S)
PL 00039/0514

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
22 February 2000

10

DATE OF REVISION OF THE TEXT
13/05/2010

11

DOSIMETRY (IF APPLICABLE)

12

INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS (IF APPLICABLE)

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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