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MEDIKINET 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
Medikinet 20 mg tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 20 mg methylphenidate hydrochloride, equivalent to 17.30 mg
methylphenidate.
Excipient with known effect: 38.48 mg lactose/tablet
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Tablet.
White, round tablet with a break score on both sides and notches at the edges
embossed with ”L” on both halves.
The tablet can be divided into equal halves.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Attention-Deficit/Hyperactivity Disorder (ADHD)
Medikinet 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 initiated under the
supervision of a specialist in childhood behaviour disorders.
Diagnosis should be made according to current DSM criteria or the guidelines in
ICD-10 and should be based on a complete history and evaluation of the patient.
Diagnosis cannot be made solely on the presence of one or more symptoms.

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 ADHD and the
decision to use the medicinal product 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
Posology
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.
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 regimen that achieves satisfactory symptom control with the lowest total daily
dose should be employed.
For doses not realisable/practicable with this strength, other strengths of this
medicinal product and other methylphenidate containing products are available.
In the treatment of hyperkinetic disorders/ADHD, the times at which the doses of
Medikinet are administered should be selected to provide the best effect when it is
most needed to combat school and social behavioural difficulties.
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 medicinal product wears off too early in the evening,
disturbed behaviour 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.
The maximum daily dose of methylphenidate hydrochloride is 60 mg.

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 medicinal product for the individual
patient with trial periods off medication to assess the patient’s functioning without
pharmacotherapy. It is recommended that methylphenidate is de-challenged at least
once yearly to assess the child’s condition (preferable during times of school
holidays). Improvement may be sustained when the medicinal product 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 with 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.

Method of administration
Oral use.
The tablets should be swallowed whole or divided into halves with the aid of liquids,
either with meals or after meals.
The effect of food on the absorption of methylphenidate from Medikinet tablets has
not been studied; therefore, a possible effect of food on absorption cannot be
excluded. Therefore it is recommended that Medikinet tablets should be taken in a
standardised manner in relation to the timing of meals, i.e. that doses should be given
at same times, relative to the time of meals, on each day, preferably with or
immediately after meals.

4.3

Contraindications


Hypersensitivity to the active substance or to any of the excipients listed in
section 6.1



Glaucoma



Phaeochromocytoma



during treatment with non-selective, irreversible monoamine oxidase (MAO)
inhibitors, or within a minimum of 14 days of discontinuing those medicinal
products, due to risk of hypertensive crisis (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

4.4



Diagnosis or history of severe and episodic (Type I) Bipolar (affective)
Disorder (that is not well-controlled)



pre-existing cardiovascular disorders including severe hypertension, heart
failure, arterial occlusive disease, angina, 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 medicinal product 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 (6 –
18 years).

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 preexisting 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 medicinal product for the individual patient with trial
periods off medication to assess the patient’s functioning without pharmacotherapy. It
is recommended that methylphenidate is de-challenged at least once yearly to assess
the child’s condition (preferably during times of school holidays). Improvement may
be sustained when the medicinal product 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, exceptional 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 is 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).

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 is
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, bearing in mind that upwards or downwards
titration may be appropriate. Treatment interruption can be considered.

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
long-term 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.

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.
Athletes must be aware that this medicinal product may cause a positive reaction to
‘anti-doping’ tests.

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.

Excipient: lactose
This medicinal product contains lactose: Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
should not take this medicine.

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 medicinal products. Therefore, caution is recommended
at combining methylphenidate with other medicinal products, 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 lenantiomers 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 medicinal products already being
taken and establish drug plasma concentrations (or for coumarin, coagulation times).

Pharmacodynamic interactions
Anti-hypertensive medicinal products
Methylphenidate may decrease the effectiveness of active substances used to treat
hypertension.

Use with medicinal products that elevate blood pressure
Caution is advised in patients being treated with methylphenidate with any other
active substance that can also elevate blood pressure (see also sections on
cardiovascular and cerebrovascular conditions in section 4.4).
Because of possible hypertensive crisis, methylphenidate is contraindicated in patients
being treated (currently or within the preceding 2 weeks) with non-selective,
irreversible MAO-inhibitors (see section 4.3).

Use with alcohol
Alcohol may exacerbate the adverse CNS effects of psychoactive active substances,
including methylphenidate. It is therefore advisable for patients to abstain from
alcohol during treatment.

Use with food
No studies have been performed to study a possible food effect. Therefore it is
recommended to take Medikinet tablets in a standardised manner in relation to the
timing of meals, i.e. that doses should be given at same times, relative to the time of
meals, on each day, preferably with or immediately after meals (see section 4.2).

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 dopaminergic active substances

Caution is recommended when administering methylphenidate with dopaminergic
active substances, 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

Fertility, pregnancy and lactation
Pregnancy
There is a limited amount of data from the use of methylphenidate in pregnant
women.
Cases of neonatal cardio-respiratory toxicity, specifically fetal tachycardia and
respiratory distress have been reported in spontaneous case reports.
Studies in animals have only shown evidence of 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.

Breast-feeding
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 can cause dizziness, drowsiness and visual disturbances including
difficulties with accommodation, diplopia and blurred vision.
Medikinet 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 Medikinet and those, which have
been reported with other methylphenidate hydrochloride formulations. If the ADRs
with Medikinet 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 (≥ 1/1,000 to <1/100)
rare (≥ 1/10,000 to <1/1,000)
very rare (<1/10,000)
not known (cannot be estimated from the available data).

Infections and infestations
Common: nasopharyngitis

Blood and lymphatic system disorders
Very rare: anaemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Not known: pancytopenia

Immune system disorders
Uncommon: hypersensitivity reactions such as angioneurotic oedema, anaphylactic
reactions, auricular swelling, bullous conditions, exfoliative conditions, urticarias,
pruritus, 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 behaviour
Uncommon: 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
Rare: mania*, disorientation, libido disorder

Very rare: suicidal attempt (including completed suicide)*, transient depressed
mood*, abnormal thinking, apathy, repetitive behaviours, over-focussing
Not known: delusions*, thought disturbances*, confusional state, dependence
Cases of abuse and dependence have been described, more often with immediaterelease formulations (frequency not known).

Nervous system disorders
Very common: headache
Common: dizziness, dyskinesia, psychomotor hyperactivity, somnolence
Uncommon: sedation, tremor
Very rare: convulsions, choreo-athetoid movements, reversible ischaemic
neurological deficit
Neuroleptic malignant syndrome (NMS; Reports were poorly documented and in
most of cases, patients were also receiving other active substances, 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
Not known: 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, diarrhoea, nausea, stomach discomfort and vomiting: These usually occur at the beginning of treatment and may be alleviated by
concomitant food intake. 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
Very rare: erythema multiforme, exfoliative dermatitis, fixed drug eruption
Not known: dry skin
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*
Not known: chest discomfort, hyperpyrexia

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
*see section 4.4
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard

4.9

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 Medikinet overdose.
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 may 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 hydrochloride has not been established.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: psychoanaleptics, psychostimulants, agents used for
ADHD and nootropics; centrally acting sympathomimetics
ATC Code: N06BA04
Mechanism of action
Medikinet is a mild CNS stimulant with more prominent effects on mental than on
motor activities. Its mode of action in man is not completely understood but its effects
are thought to be due to cortical stimulation and possibly to stimulation of the
reticular activating system.
The mechanism by which Medikinet exerts its mental and behavioural effects in
children is not clearly established, nor is there conclusive evidence showing how
these effects relate to the condition of the central nervous system. It is thought to
block the re-uptake of norepinephrine and dopamine into the presynaptic neurone and
increase the release of these monoamines into the extraneuronal space. Medikinet is a
racemic mixture of the d- and l-threo enantiomers of methylphenidate. The denantiomer is more pharmacologically active than the l-enantiomer.

5.2

Pharmacokinetic properties
Absorption
Medikinet is rapidly and almost completely absorbed. Owing to its pronounced “firstpass” metabolism the absolute bioavailability is low at only 30% (11-51%) of the
dose. Absorption is accelerated when the medicinal product is taken with meals but
has no effect on the total amount absorbed. Maximum plasma concentrations of 7
ng/ml are reached on average 1-2 hours after administration of 10 mg. The maximum
plasma concentrations vary considerably interindividually.
There are considerable interindividual and intraindividual variations in the plasma
concentrations which, however, provide little conclusive evidence of the therapeutic
efficacy. The relatively short half-life correlates well with the duration of action of 1
to 4 hours.

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-binding (10-33%). The volume of distribution after a single
intravenous dose is 2.2 l/kg (2.65±1.1 l/kg for d-methylphenidate and 1.8±0.9 l/kg for
l-methylphenidate).

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 l/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 an average half-life of
approximately 2 hours. The mean clearance after an intravenous single dose is 0.565
l/h/kg (0.40± 0.12 l/h/kg for d-methylphenidate and 0.73±0.28 l/h/kg for lmethylphenidate). After oral administration, approximately 78-97% of the dose is
excreted within 48 to 96 h via the urine and 1 to 3% via the faeces in the form of
metabolites. Only small amounts (< 1%) of unchanged methylphenidate appear in the
urine. A large proportion of an intravenous dose (89%) is eliminated in the urine
within 16 hours, presumably regardless of the pH value, as ritalinic acid.
There is apparently no difference in the pharmacokinetics of methylphenidate
between children with hyperkinetic disorders/ ADHD and healthy adult test subjects.
Pharmacokinetic properties of methylphenidate have not been studied in children
below 6 years of age or in elderly above 65 years.
The renal elimination of ritalinic acid may decrease in the case of impaired renal
function.
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/foetal development
Methylphenidate is not considered to be teratogenic in rats and rabbits. Foetal 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
Microcristalline cellulose
Pregelatinised maize starch
Calcium hydrogen phosphate dihydrate
Lactose monohydrate
Magnesium stearate

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
3 years

6.4

Special precautions for storage
Do not store above 25 °C.
Store in the original package in order to protect from moisture.

6.5

Nature and contents of the container
Pack sizes 30 or 50 tablets
Boxes containing tablets packaged in PVC/PE/PVdC white opaque blisters heat
sealed to aluminium foil.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER

Medice Arzneimittel Pütter GmbH & Co. KG
Kuhloweg 37
58638 Iserlohn
Germany

8

MARKETING AUTHORISATION NUMBER(S)
PL 11243/0004

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
11/11/2013

10

DATE OF REVISION OF THE TEXT
11/11/2013

11

DOSIMETRY (IF APPLICABLE)

12

INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS (IF APPLICABLE)

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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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