Concerta Extended Release Tablets

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Methylphenidate hydrochloride 27 mg
Available from:
Janssen-Cilag (New Zealand) Ltd
INN (International Name):
Methylphenidate hydrochloride 27 mg
Dosage:
27 mg
Pharmaceutical form:
Modified release tablet
Composition:
Active: Methylphenidate hydrochloride 27 mg Excipient: Butylated hydroxytoluene Cellulose acetate Hypromellose Caranuba Wax Iron oxide black Iron oxide red Iron oxide yellow Opacode black NS-78-17715 Opadry Clear YS-1-19025-A Opadry grey Y-30-17528 Phosphoric acid Poloxamer Polyethylene oxide Povidone Sodium chloride Stearic acid Succinic acid
Units in package:
Bottle, plastic, HDPE botle with polypropylene screw on CRC 28 tablets, 28 tablets
Class:
Class B2 Controlled Drug
Prescription type:
Class B2 Controlled Drug
Manufactured by:
Janssen Pharmaceuticals Inc
Therapeutic indications:
CONCERTA is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. Need for comprehensive treatment programme: CONCERTA is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational and social) for patients with this syndrome. Stimulants are not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the patient's symptoms. Long term use: The effecti
Product summary:
Package - Contents - Shelf Life: Bottle, plastic, HDPE botle with polypropylene screw on CRC - 28 tablets - 24 months from date of manufacture stored at or below 25°C - Bottle, plastic, HDPE botle with polypropylene screw on CRC - 30 tablets - 24 months from date of manufacture stored at or below 25°C - Bottle, plastic, HDPE botle with polypropylene screw on CRC - 56 tablets - 24 months from date of manufacture stored at or below 25°C - Bottle, plastic, HDPE botle with polypropylene screw on CRC - 60 tablets - 24 months from date of manufacture stored at or below 25°C - Bottle, plastic, HDPE botle with polypropylene screw on CRC - 100 tablets - 24 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-6899c
Authorization date:
2005-12-23

CONCERTA

(190110) ACMI

CONCERTA

®

extended-release tablets

Methylphenidate hydrochloride

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about CONCERTA

extended-release tablets. It does not

contain all the available information.

It does not take the place of talking to

your doctor or pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you or your child taking

CONCERTA against the benefits this

medicine is expected to have for you

or your child.

If you have any concerns about

taking CONCERTA ask your doctor

or pharmacist.

Keep this leaflet with your medicine.

You may need to read it again.

What is CONCERTA

used for

CONCERTA is used to treat

Attention Deficit Hyperactivity

Disorder (ADHD). CONCERTA is

part of a comprehensive treatment

program which usually includes

psychological, educational and social

therapy.

CONCERTA is a stimulant that

increases attention and decreases

impulsiveness and hyperactivity in

patients with ADHD.

CONCERTA should be used as part

of a total treatment program for

ADHD that may include counselling

or other therapies.

CONCERTA is not recommended

for use in children less than 6 years

and elderly over 65 years because it

has not been studied in these age

groups.

CONCERTA tablets are made in an

extended release form. This means

that they release the active ingredient

slowly. The outer layer of the

CONCERTA tablet dissolves right

after it is swallowed in the morning,

giving an initial dose of

methylphenidate hydrochloride.

The tablets have a special shell that

allows the rest of the

methylphenidate hydrochloride to be

released from the tablet at a slow rate

throughout the day.

The tablet shell does not dissolve

completely after all the drug has been

released and sometimes the tablet

shell may be seen in your stool. This

is normal.

Your doctor may have prescribed

CONCERTA for another reason.

Ask your doctor if you have any

questions about why this medicine

has been prescribed for you/your

child.

CONCERTA can be abused or

lead to dependence. Keep

CONCERTA in a safe place to

prevent misuse and abuse.

Before you take

CONCERTA

When you must not take it

Do not take CONCERTA if

you/your child have an allergy to:

methylphenidate hydrochloride

(the active ingredient in

CONCERTA) or

any of the other ingredients in

CONCERTA. See Product

Description at the end of this

leaflet for a list of ingredients.

Symptoms of an allergic reaction

may include: rash, itching or hives on

the skin; shortness of breath,

wheezing or difficulty breathing;

swelling of the face, lips, tongue or

other parts of the body.

Do not take CONCERTA if

you/your child have any of the

following medical conditions:

overactive thyroid gland

heart problems, including angina

(chest pain), irregular heart beat

that is potentially life-threatening

and high blood pressure

(untreated or not under control)

a problem with the blood vessels

in your brain (such as an

aneurysm or a stroke)

severe depression, anorexia

nervosa, suicidal tendency,

bipolar disorder or other mental

illness

currently taking or have taken a

monoamine oxidase (MAO)

CONCERTA

(190110) ACMI

inhibitor, medicines used to treat

major depression (eg.

phenelzine, tranylcypromine) or

medicines used in Parkinson's

disease (eg. selegiline) within the

last 14 days

phaeochromocytoma (a tumour of

the adrenal gland)

have a history of drug or alcohol

abuse

Do not use CONCERTA if the

packaging is torn or shows signs of

tampering.

Do not use CONCERTA beyond

the expiry date (month and year)

printed on the pack.

If you/your child take CONCERTA

after the expiry date it may not work.

Before you/your child start

to take it

You must tell your doctor if you/your

child:

are/is pregnant or planning to

become pregnant

are/is breastfeeding or wish to

breastfeed.

The active ingredient in

CONCERTA passes into breast

milk and there is a possibility that

your baby may be affected. Your

doctor can discuss with you the

risks and benefits involved

are/is or have/has been alcohol or

drug dependent

have/has seizures or fits

have/has heart problems

Heart-related problems including

sudden death in patients who

have heart problems or heart

defects, stroke and heart attack in

adults and increased blood

pressure and heart rate have been

reported with the use of

methylphenidate, the active

ingredient in CONCERTA.

have / had thoughts about suicide

or attempted suicide

have/has high blood pressure

have/has aggressive behaviour or

hostility

have/has a narrowing or blockage

in your digestive tract (stomach,

small or large intestine)

Tourette's syndrome (tics) or a

family history of this disorder

have a problem with the blood

vessels in your brain (such as an

aneurysm)

have/has eye problems, such as

increased pressure in the eye, a

condition called "glaucoma" or

long-sightedness (difficulty

seeing near objects)

have/has liver or kidney problems

have/has mental problems

including psychosis, mania,

bipolar illness, or depression.

Mental (Psychiatric) problems

may develop or get worse,

including behaviour and thought

problems, bipolar illness,

aggressive behaviour or hostility.

Your doctor may need to adjust the

dose or adapt your treatment if

you/your child have any of these

conditions.

If you have not told your doctor or

pharmacist about any of the above,

tell them before you/your child

start taking CONCERTA.

Taking other medicines:

Tell your doctor or pharmacist if

you/your child are taking any other

medicines, including medicines you

can buy without a prescription from a

pharmacy, supermarket or health

food shop.

In particular, tell your doctor or

pharmacist if you/your child are

taking any of the following:

Monoamine oxidase (MAO)

inhibitors such as phenelzine,

selegiline

medicines that increase blood

pressure

medicines used to treat high

blood pressure

medicines used to treat

depression or anxiety such as

venlafaxine, sertraline,

amitriptyline and imipramine

medicines used to prevent

seizures such as phenytoin,

phenobarbitone, and primidone

and valproate.

Antipsychotic medicines such as

olanzapine, risperidone and

quetiapine used to improve the

symptoms of certain types of

mental illness, e.g. schizophrenia

and bipolar disorder.

These medicines may be affected

by CONCERTA or may affect

how well CONCERTA works.

Your doctor or pharmacist can

tell you what to do if you/your

child are taking any of these

medicines.

Taking CONCERTA

Follow the directions given to you

by your doctor and pharmacist.

These directions may differ from the

information contained in this leaflet.

How much to take:

If you/your child are currently

taking other formulations of

methylphenidate, your doctor will

decide the best starting dose

Children and Adolescents

The starting dose is one

CONCERTA 18 mg extended-

release tablet in the morning

The maximum dose is 54 mg a

day taken as one dose for children

aged between 6-12 years and 72

mg a day taken as one dose for

adolescents aged between 13-18

years.

Adults

The starting dose is one

CONCERTA 18 mg or 36 mg

extended-release tablet in the

morning

The maximum dose is 72 mg a

day taken as one dose.

CONCERTA

(190110) ACMI

How to take it:

CONCERTA should be

swallowed whole with a glass of

liquid. It should not be chewed,

broken or crushed

CONCERTA may be taken with

or without food.

If you do not understand the

instructions provided with this

medicine, ask your doctor or

pharmacist for help.

If you/your child forget to

take it

It may be best to wait until the

following morning to take the

next dose. Remember the effects

of CONCERTA are designed to

last approximately 12 hours from

the time it is taken.

Do not take or give your child a

double dose to make up for the

dose missed.

If you/your child have missed more

than one dose, or are not sure what

to do, check with your doctor or

pharmacist.

If you have trouble remembering

when to take your medicine, ask your

pharmacist for some hints.

If you/your child have taken

too much (overdose)

Immediately telephone your doctor

or the Poisons Information Centre for

advice, or go to Accident and

Emergency at your nearest hospital.

Do this even if there are no signs of

discomfort or poisoning. You/your

child may need urgent medical

attention.

Poisons Information Centre

telephone number:0800 POISON or

0800 764 766

Keep this telephone number handy.

If you/your child take too much

CONCERTA you/your child may

experience symptoms such as

vomiting, agitation, muscle

twitching, hallucination, dry mouth,

excessive sweating, headache,

irregular heart beat, dilated pupils,

convulsions/fits, breathing problems,

confusion and seizures.

While you are taking

CONCERTA

Things you must do

Always follow your doctor's

instructions carefully

Take CONCERTA exactly as

your doctor has prescribed. Like

all stimulants, CONCERTA may

become habit-forming and can be

abused by some people. If

you/your child take it correctly as

instructed by your doctor, abuse

or dependence should not be a

problem, either now or later in

life

Be sure to keep all of your

doctor's appointments so that

your/your child's progress can be

checked

Your doctor will want to check

your/your child's blood pressure

and pulse and do blood test from

time to time to prevent unwanted

side effects from happening

Tell your doctor if you become

pregnant while taking

CONCERTA

Parents and/or caregivers should

be alert for the development of

thoughts or acts of self-harm,

hallucinations, abnormal thinking

(psychosis) or new or worsening

hostility. These were uncommon

symptoms seen in clinical studies

with CONCERTA and it is not

known if they were caused by

CONCERTA. Contact your/your

child's doctor or mental health

professional straight away or seek

urgent medical attention if these

occur

Tell your doctor if you or your

child become aggressive, anxious

or agitated, or feel more

aggressive, anxious or agitated

than usual

Parents and/or caregivers should

contact their/their child's doctor

or seek urgent treatment if

they/their child develops chest

pain, tightness in the chest,

shortness of breath, irregular

heart beat, feeling faint or loss of

consciousness while taking

CONCERTA

Tell your doctor if you or your

child develop severe headaches,

weakness or paralysis of any

body part, or develop problems

with coordination, vision,

speaking, finding words or with

your memory

Children should have their height

and weight checked regularly as

CONCERTA may slow children's

rate of growth

Tell your doctor if you/your child

experience numbness, tingling

and a changing colour of the

fingers and toes when cold

(‘Raynaud’s phenomenon’)

Tell your doctor if you or your

child develop prolonged and

painful erections, seek immediate

medical attention

Tell your doctor if you/your child

are about to start taking a new

medicine, tell your doctor and

pharmacist that you/your child

are taking CONCERTA

Tell your doctor if you/your child

are about to have an operation as

CONCERTA should not be used

on the day of the operation

Things you must not do

Do not drink alcohol whilst you

are being treated with

CONCERTA as it may increase

the risk of side effects

Do not use CONCERTA to treat

any other complaint unless your

doctor says so.

Do not give this medicine to

anyone else, even if their

symptoms seem similar.

Do not stop treatment without

first checking with your doctor.

CONCERTA

(190110) ACMI

If you/your child suddenly stop

taking this medicine, you/your

child's condition may reappear or

you/your child may get unwanted

effects such as depression. Your

doctor may want to gradually

reduce the amount of medicine

taken each day before stopping it

completely.

Things to be careful of

CONCERTA may impair your

ability to operate potentially

hazardous machinery or vehicles.

You should exercise caution until

you are reasonably certain how

you react to CONCERTA before

you drive a car, operate

machinery, or do anything else

that could be dangerous.

Side Effects

All medicines can have side effects.

Sometimes they are serious, most of

the time they are not. You/your child

may need medical treatment if you

get some side effects. Do not be

alarmed by this list of possible side

effects. You/your child may not

experience any of them.

Ask your doctor or pharmacist to

answer any questions you may

have. Tell your doctor if you/your

child experience any of the

following and they worry you:

stomach or bowel problems such

as:

loss of appetite

stomach pain

nausea

vomiting

dry mouth

indigestion

constipation

weight loss

diarrhoea

difficulty thinking or working

because of:

headache

trouble sleeping

dizziness

throat or lung infections such as:

cold

cough

sore throat and hoarse/ loss of

voice

feeling of tension or fullness in

the nose, cheeks and behind your

eyes, sometimes with a throbbing

ache, fever, stuffy nose and loss

of the sense of smell

joints or movement changes such

as:

painful and/ or swollen joints

aching muscles, muscle tightness,

spasm, tenderness or weakness,

not caused by exercise

clenching or grinding the teeth

other changes such as:

decreased sex drive

feeling very tired or weak

Tell your doctor immediately if

you notice any of the following:

behavioural changes such as:

aggression

confusion

disorientation

seeing, feeling or hearing things

that are not there

mood swings, overexcitement

over-activity and uninhibited

behaviour

feeling depressed

feeling tense

nervousness or anxiety

brief periods of acute anxiety

where symptoms being suddenly

and usually include difficulty

breathing, chest pains, fast heart

rate, dizziness and

lightheadedness, sweating,

trembling and faintness

restlessness

agitation and irritability

movements or sounds that you

cannot control (tics)

nervous system changes such as:

convulsions, fits or seizures

muscle twitching

numbness and tingling feeling in

fingers and toes

reproductive system changes such

as:

prolonged and painful erections

difficulty getting and keeping an

erection

changes in your sight, namely:

visual disturbance

blurred or double vision

dilated pupils

changes to the skin or hair such as:

unusual hair loss or thinning of

the hair

redness of the skin

excessive sweating

signs of allergy such rash, itching

or hives on the skin; shortness of

breath, wheezing or difficulty

breathing; swelling of the face,

lips, tongue or other parts of the

body

body temperature changes such as:

fever

hot flushes

heart or blood problems such as:

fast or abnormal heart beat

increased blood pressure

chest pain

chest discomfort

low white blood cell count

low platelet count

other side effects such as:

shortness of breath

slowing of growth (height and

weight) in children

blockage of the oesophagus,

stomach, small or large intestine

in patients who already have a

narrowing in any of these organs

increased levels of the liver

enzyme ALT

CONCERTA

(190110) ACMI

Other side effects not listed above

may also occur in some people. Tell

your doctor if you notice any other

effects.

After using

CONCERTA

Storage

Keep the tablets in the bottle until it

is time to take them.

Store CONCERTA in a cool dry

place where the temperature is below

25°C. Keep the container tightly

closed.

Keep medicines where children

cannot reach them.

A locked cupboard at least one-and-

a-half metres (1.5 m) above the

ground is a good place to store

medicines.

Do not store CONCERTA, or any

other medicine, in the bathroom or

near a sink. Do not leave medicines

in the car or on windowsills. Heat

and dampness can destroy some

medicines.

Disposal

If your doctor tells you/your child to

stop taking CONCERTA extended-

release tablets or the medicine has

passed its expiry date, ask your

pharmacist what to do with any

medicine that may be left over.

Product Description

What it looks like

CONCERTA 18 mg are yellow

capsule-shaped tablets, with "alza

18" printed in black ink on one side.

CONCERTA 27 mg are grey

capsule-shaped tablets, with "alza

27" printed in black ink on one side.

CONCERTA 36 mg are white

capsule-shaped tablets, with "alza

36" printed in black ink on one side.

CONCERTA 54 mg are brownish-

red capsule-shaped tablets, with "alza

54" printed in black ink on one side.

Ingredients

Each CONCERTA extended-release

tablet contains 18 mg, 27 mg, 36 mg

or 54 mg of methylphenidate

hydrochloride as the active

ingredient.

Each tablet also contains the

following other ingredients:

butylated hydroxytoluene, carnauba

wax, cellulose acetate, hypromellose,

Opacode black NS-78-17715,

Opadry clear YS-1-19025-A,

phosphoric acid, poloxamer,

polyethylene oxide, povidone,

sodium chloride, stearic acid,

succinic acid and synthetic iron

oxides. The 18 mg tablet also

contains Opadry II yellow YS-30-

12788-A. The 27 mg tablet also

contains Opadry II grey Y-30-17528.

The 36 mg tablet also contains

Opadry II white Y-30-18037. The 54

mg tablet also contains Opadry II red

Y-30-15567-A.

CONCERTA extended-release

tablets contain lactose.

Sponsor

JANSSEN-CILAG Pty Ltd

1-5 Khartoum Road

Macquarie Park NSW 2113 Australia

Telephone: 1800 226 334

NZ Office: Auckland New Zealand

Telephone: 0800 800 806

This leaflet was prepared in January

2019.

CCDS181023

Page 1 of 18

CONCERTA(181127)ADS

CONCERTA

®

DATA SHEET

1.

PRODUCT NAME

CONCERTA

Extended – Release Tablets 18 mg methylphenidate hydrochloride modified release tablet

CONCERTA

Extended – Release Tablets 27 mg methylphenidate hydrochloride modified release tablet

CONCERTA

Extended – Release Tablets 36 mg methylphenidate hydrochloride modified release tablet

CONCERTA

Extended – Release Tablets 54 mg methylphenidate hydrochloride modified release tablet

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

One extended release tablet contains 18 mg, 27 mg, 36 mg or 54 mg of methylphenidate hydrochloride.

Excipient(s) with known effect:

Lactose

For the full list of excipients, see

section 6.1 List of excipients

3.

PHARMACEUTICAL FORM

CONCERTA is available as an extended-release tablet for once-a-day oral administration containing 18, 27, 36

or 54 mg methylphenidate hydrochloride. It is designed to have a 12-hour duration of effect.

CONCERTA 18 mg are yellow capsule-shaped tablets, with “alza 18” printed in black ink on one side.

CONCERTA 36 mg are white capsule-shaped tablets, with “alza 36” printed in black ink on one side.

CONCERTA 27 mg are grey capsule-shaped tablets, with “alza 27” printed in black ink on one side.

CONCERTA 54 mg are brownish-red capsule-shaped tablets, with “alza 54” printed in black ink on one side.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications

CONCERTA is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).

A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of hyperactive-

impulsive or inattentive symptoms that caused impairment and were present before age 7 years.

Need for comprehensive treatment programme:

CONCERTA is indicated as an integral part of a total

treatment program for ADHD that may include other measures (psychological, educational and social) for

patients with this syndrome. Stimulants are not intended for use in the patient who exhibits symptoms secondary

environmental factors and/or

other

primary

psychiatric

disorders, including

psychosis.

Appropriate

educational placement is essential and psychosocial intervention is often helpful. When remedial measures

alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician’s

assessment of the chronicity and severity of the patient’s symptoms.

Long term use:

The effectiveness of CONCERTA for long-term use has not been systematically evaluated in

controlled trials. Therefore the physician who elects to use CONCERTA for extended periods should

periodically re-evaluate the long-term usefulness of the drug for the individual patient.

CCDS181023

Page 2 of 18

CONCERTA(181127)ADS

4.2.

Dose and method of administration

CONCERTA is administered orally once daily and should be taken in the morning.

CONCERTA must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed.

CONCERTA may be administered with or without food.

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

accurate

recording

pre-treatment

height

weight

growth

chart

(see

section

4.3

Contraindications

section 4.4 Special warnings and precautions for use

Ongoing monitoring:

Growth, psychiatric and cardiovascular status should be continuously monitored (see also

section 4.4 Special

warnings and precautions for use

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.

Dose

Children (over 6 years of age) and adolescents:

Dosage may be adjusted in 9 mg increments between 18 mg and 36mg and consecutively in 18 mg increments

to a maximum of 54 mg/day for children aged between 6-12 years and to a maximum of 72 mg/day for

adolescents aged between 13-18 years. In general, dosage adjustment may proceed at approximately weekly

intervals.

Adults:

Dosage can be adjusted from an initial dose of 18 or 36 mg/day in 18mg increments to a maximum of 72mg/day

taken once daily in the morning. In general, dosage adjustment may proceed at approximately weekly intervals.

Patients respond at different dose levels and CONCERTA must be titrated to effect on an individual patient

needs and response basis. A maximum dose of 108 mg/day have been included in clinical trials (see

Clinical

Trials

Patients New to Methylphenidate

: The recommended starting dose of CONCERTA for patients who are not

currently taking methylphenidate, or for patients who are on stimulants other than methylphenidate, is 18 mg

once daily for children and adolescents and 18 or 36 mg once daily for adults.

Patients Currently Using Methylphenidate

: The recommended dose of CONCERTA for patients who are

currently taking methylphenidate two or three times daily at doses of 10 – 60 mg per day is provided in

Table

1

CCDS181023

Page 3 of 18

CONCERTA(181127)ADS

Table 1: Recommended dose conversions from methylphenidate regimens to CONCERTA

Previous methylphenidate daily dose

Recommended CONCERTA starting dose

5 mg methylphenidate three times daily

18 mg every morning

10 mg methylphenidate three times daily

36 mg every morning

15 mg methylphenidate three times daily

54 mg every morning

20 mg methylphenidate three times daily

72 mg every morning

Clinical judgement should be used when selecting the dose for patients currently taking methylphenidate in other

regimens. Daily dosage above 54 mg is not recommended for children aged between 6-12 years. Daily dosage

above 72 mg is not recommended for adolescents aged between 13-18 years.

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 de-challenged 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.

Special Populations

Use in Infants and children

Use of CONCERTA in patients under six years of age has not been studied in controlled trials. CONCERTA

should not be used in patients under six years old.

Use in Elderly

Use of CONCERTA in patients over 65 years of age has not been studied in controlled trials.

Method of administration

CONCERTA must be swallowed whole with the aid of liquids.

Tablets should not be chewed, divided or crushed.

The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The

tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned

if they occasionally notice in their stool something that looks like a tablet.

4.3.

Contraindications

CONCERTA is contraindicated:

in patients with known hypersensitivity to methylphenidate or any inactive ingredient used in this product

(see

section 6.1 List of excipients

during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following

discontinuation of a monoamine oxidase inhibitor (hypertensive crises may result);

in patients with hyperthyroidism;

Phaeochromocytoma;

CCDS181023

Page 4 of 18

CONCERTA(181127)ADS

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);

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.

4.4.

Special warnings and precautions for use

Use with caution in the following circumstances

Depression and Psychosis

CONCERTA should not be used to treat severe depression or for the prevention or treatment of normal fatigue

states.

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.

In psychotic patients administration of methylphenidate may exacerbate symptoms of behaviour disturbance and

thought disorder.

Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking or mania in patients

without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such

symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of

treatment may be appropriate.

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.

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

mixed/manic

episode

such

patients.

Prior

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

Depression and Psychosis

above and

section 4.2 Dose and method of administration

). Patients

should be monitored for symptoms at every adjustment of dose, then at least every 6 months and at every visit.

CCDS181023

Page 5 of 18

CONCERTA(181127)ADS

Tics and worsening of Tourette’s syndrome

Methylphenidate is associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s

syndrome has also been reported. It is recommended that the family history be assessed, and that the patient is

clinically evaluated for tics or Tourette’s syndrome before initiating methylphenidate. Regular monitoring for

the emergence or worsening of tics or Tourette’s syndrome during treatment with methylphenidate is

recommended at every dose adjustment and every visit, and treatment discontinued if clinically appropriate.

Drug Dependence

Patients should be carefully monitored for the risk of diversion, misuse and abuse of methylphenidate.

CONCERTA should be given cautiously to patients with a history of drug or alcohol dependence. Chronic

abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal

behaviour.

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.

Careful supervision is required during withdrawal from abusive use since severe depression may occur.

Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may

require follow-up.

Drug Screening

CONCERTA contains methylphenidate which may induce a false positive laboratory test for amphetamines,

particularly with immunoassay screen test.

Potential for Gastrointestinal Obstruction

CONCERTA tablet is non-deformable and does not appreciably change in shape in the GIT. It should not

ordinarily be administered to patients with pre-existing severe GI narrowing (pathologic or iatrogenic) or in

patients with dysphagia or significant difficulty in swallowing tablets. Due to the prolonged-release design of

the tablet, CONCERTA should only be used in patients who are able to swallow the tablet whole.

Sudden Death and Pre-existing Structural Cardiac Abnormalities

Although a causal relationship has not been established, sudden death has been reported in patients with

structural cardiac abnormalities treated with ADHD drugs with stimulant effects. These treatments should be

used with caution in patients with structural cardiac 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.

Hypertension and Cardiovascular Conditions

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.

In the laboratory clinical trials in children both CONCERTA and methylphenidate three times daily increased

resting pulse by an average of 2 to 6 bpm and produced average increases of systolic and diastolic blood pressure

of roughly 1 to 4 mm Hg during the day, relative to placebo. In placebo-controlled studies in adults, mean

increases in resting pulse rate of approximately 4 to 6 bpm were observed with CONCERTA at endpoint vs. a

CCDS181023

Page 6 of 18

CONCERTA(181127)ADS

mean change of roughly -2 to 3 bpm with placebo. Mean changes in blood pressure at endpoint ranged from

about -1 to 1 mm Hg (systolic) and 0 to 1 mm Hg (diastolic) for CONCERTA and from -1 to 1 mm Hg (systolic)

and -2 to 0 mm Hg (diastolic) for placebo. Therefore, caution is indicated in treating patients whose underlying

medical conditions might be compromised by increases in blood pressure or heart rate.

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

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

section 4.3 Contraindications

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.

Priapism

Prolonged

painful

erections

requiring

immediate

medical

attention

(sometimes

including

surgical

intervention, have been reported with methylphenidate products, including CONCERTA, in both paediatric and

adult patients (see

section 4.8 Undesirable effects

). Priapism can develop after some time on methylphenidate,

often subsequent to an increase in dose. Priapism has also appeared during a period of methylphenidate

withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained erections or

frequent and painful erections should seek immediate medical attention.

Cerebrovascular disorders

Cerebrovascular disorders (including cerebral vasculitis and cerebral hemorrhage) have been reported with the

use of CONCERTA (see

section 4.8 Undesirable effects

). Consider cerebrovascular disorders as a possible

diagnosis in any patient who develops new neurological symptoms that are consistent with cerebral ischemia

during CONCERTA therapy. These symptoms could include severe headache, unilateral weakness or paralysis,

and impairment of coordination, vision, speech, language, or memory. If a cerebrovascular disorder is suspected

during treatment, discontinue CONCERTA immediately. Early diagnosis may guide subsequent treatment.

In patients with pre-existing cerebrovascular disorders (e.g., aneurysm, vascular malformations/anomalies),

treatment with CONCERTA is not recommended.

Aggression, anxiety and agitation

Aggressive behaviour, marked anxiety, or agitation are often observed in patients with ADHD, and have been

reported

patients

treated

with

CONCERTA

(see

section

4.8

Undesirable

effects

Anxiety

discontinuation of CONCERTA in some patients. It is recommended to monitor patients beginning treatment

with CONCERTA for the appearance of, or worsening of, aggressive behaviour, marked anxiety, or agitation.

CCDS181023

Page 7 of 18

CONCERTA(181127)ADS

Haematologic Monitoring

Periodic full blood count, differential and platelet counts are advised during prolonged therapy.

Increased intraocular pressure and glaucoma

There have been reports of a transient elevation of intraocular pressure (IOP) associated with methylphenidate

treatment. It is recommended to prescribe CONCERTA to patients with open-angle glaucoma or abnormally

increased IOP only if the benefit of treatment is considered to outweigh the risk. Patients with a history of

abnormally increased IOP or open-angle glaucoma, and patients at risk for acute angle-closure glaucoma (e.g.,

patients with significant hyperopia) must be closely monitored.

CONCERTA is not recommended in patients with acute angle-closure glaucoma.

Use in patients with renal impairment

There is no experience with the use of CONCERTA in patients with renal insufficiency. After oral

administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and

approximately 80% of the radioactivity was excreted in the urine in the form of PPAA. Since renal clearance is

not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the

pharmacokinetics of CONCERTA.

Use in patients with hepatic impairment

There is no experience with the use of CONCERTA in patients with hepatic insufficiency.

Use in children

The safety and efficacy of CONCERTA in children under 6 years old have not been established.

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 under

section 4.2

Dose and method of administration

section 4.4 Special warnings and

precautions for use

for hypertension and cardiovascular conditions, 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

spontaneity,

withdrawal

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 de-challenged 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.

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.

Use in the elderly

Methylphenidate should not be used in the elderly. Safety and efficacy has not been established in this age group.

CCDS181023

Page 8 of 18

CONCERTA(181127)ADS

4.5.

Interactions with other medicines and other forms of interaction

Pharmacokinetic interaction:

It is not known how methylphenidate may effect 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.

Pharmacodynamic interactions:

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 Special warnings

and precautions for use)

Because of possible hypertensive crisis, methylphenidate is contraindicated in patients being treated (currently

within

preceding

weeks)

with

non-selective,

irreversible

MAO-inhibitors

(see

section

4.3

Contraindications

Anti-hypertensive drugs

Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.

Use with alcohol

Alcohol may exacerbate the adverse CNS effects 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 domapinergic drugs

Caution

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.

Use with serotonergic drugs

There

have

been

reports

serotonin

syndrome

following

coadministration

methylphenidate

with

serotonergic drugs. If concomitant use of CONCERTA with a serotonergic drug is warranted, prompt

recognition of the symptoms of serotonin syndrome is important. CONCERTA must be discontinued as soon as

possible if serotonin syndrome is suspected.

Use with antipsychotic drugs

Because a predominant action of methylphenidate is to increase extracellular dopamine levels, CONCERTA

may be associated with pharmacodynamic interactions when co-administered with some antipsychotics. Caution

is warranted in patients receiving both CONCERTA and an antipsychotic, as extrapyramidal symptoms could

emerge when these drugs are administered concomitantly or when adjusting the dosage of one or both drugs.

CCDS181023

Page 9 of 18

CONCERTA(181127)ADS

4.6.

Fertility, pregnancy and lactation

Use in pregnancy -

Category B3

The safety of methylphenidate for use during human pregnancy has not been established, and no studies are

available on the use of CONCERTA in pregnant women. CONCERTA should be used during pregnancy only

if the potential benefit justifies the potential risk.

There is a 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.

Oral administration of methylphenidate to rabbits during the period of organogenesis has produced teratogenic

effects at doses of 200 mg/kg/day, associated with systemic exposure (plasma AUC) approximately 5-6 fold that

in humans receiving the maximal recommended dose. The exposure at the no-effect dose in rabbits

(60 mg/kg/day) was less than human exposure. Teratogenic effects were not seen in rats at oral methylphenidate

doses up to 75 mg/kg/day, associated with systemic exposure of 21-25 fold that in humans receiving the maximal

dose. Oral administration of methylphenidate to rats from early pregnancy until weaning was associated with

maternal toxicity, reduced offspring weight and marginal alterations in neuromotor performance in offspring at

a maternal dose of 30 mg/kg/day, approximately 3-6 fold the maximum recommended clinical dose on a mg/m

basis.

Breast-feeding

Methylphenidate has been detected in human milk. Based on breast milk sampling from five mothers,

methylphenidate concentrations in human milk resulted in infant doses of 0.16% to 0.7% of the maternal

weight-adjusted dosage, and a milk to maternal plasma ratio ranging between 1.1 and 2.7. Caution should be

exercised if CONCERTA is administered to a breast-feeding woman.

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.

Oral administration of methylphenidate to rats from early pregnancy until weaning was associated with maternal

toxicity, reduced offspring weight and marginal alterations in neuromotor performance in offspring at a maternal

dose of 30 mg/kg/day, approximately 3-6 fold the maximum recommended clinical dose on a mg/m

basis.

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.

Effect on ability to drive or operate machinery

Methylphenidate

cause

dizziness,

drowsiness

visual

disturbances

including

difficulties

with

accommodation, diplopia and blurred vision and may impair the ability of the patient to operate potentially

hazardous machinery or vehicles. Patients should be cautioned accordingly until they are reasonably certain that

CONCERTA does not adversely affect their ability to engage in such activities.

4.8.

Undesirable effects

Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were

considered to be reasonably associated with the use of methylphenidate based on the comprehensive assessment

of the available adverse event information. A causal relationship with methylphenidate cannot be reliably

established in individual cases. Further, because clinical trials are conducted under widely varying conditions,

adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical

trials of another drug and may not reflect the rates observed in clinical practice.

Clinical Trial Data

Double-Blind Data – Adverse Drug Reactions Reported at

1% Frequency

CCDS181023

Page 10 of 18

CONCERTA(181127)ADS

Adverse Drug Reactions (ADRs) in either the paediatric or adult double-blind studies (

Table 2 and Table 3

may be relevant for both patient populations.

Paediatric Patients

The safety of CONCERTA was evaluated in 639 paediatric patients (children and adolescents) with ADHD who

participated in 4 placebo-controlled, double-blind clinical trials. The information presented in this section was

derived from pooled data.

Adverse Drug Reactions (ADRs) reported by

1% of CONCERTA-treated children and adolescent subjects and

more frequently than placebo in these trials are shown in

Table 2

Table 2. Adverse Drug Reactions Reported by

1% of CONCERTA-Treated Children and

Adolescent Subjects and More Frequently than Placebo in 4 Placebo-Controlled, Double-

Blind Clinical Trials

System/Organ Class

Adverse Drug Reaction

CONCERTA

(n=321)

%

Placebo

(n=318)

%

Infections and Infestations

Nasopharyngitis

Psychiatric Disorders

Insomnia

Nervous System Disorders

Headache

10.6

11.9

Dizziness

Respiratory, Thoracic and Mediastinal Disorders

Cough

Oropharyngeal Pain

Gastrointestinal Disorders

Abdominal Pain upper

Vomiting

General Disorders and Administration Site Conditions

Pyrexia

*Terms of Initial insomnia (CONCERTA=0.6%) and Insomnia (CONCERTA=2.2%) are combined into

Insomnia

The majority of ADRs were mild to moderate in severity.

Adult Patients

The safety of CONCERTA was evaluated in 905 adult subjects with ADHD who participated in 3 placebo-

controlled, double-blind clinical trials. The information presented in this section was derived from pooled data.

Adverse Drug Reactions (ADRs) reported by

1% of CONCERTA-treated adult subjects in these trials are

shown in

Table 3

Table 3. Adverse Drug Reactions Reported by

1% of CONCERTA-Treated Adult Subjects in

3 Placebo-Controlled, Double-Blind Clinical Trials

System/Organ Class

Adverse Drug Reaction

CONCERTA

(n=596)

%

Placebo

(n=309)

%

Infections and Infestations

Upper respiratory tract infection

Sinusitis

Metabolism and Nutrition Disorders

Decreased appetite

24.8

Anorexia

CCDS181023

Page 11 of 18

CONCERTA(181127)ADS

System/Organ Class

Adverse Drug Reaction

CONCERTA

(n=596)

%

Placebo

(n=309)

%

Psychiatric Disorders

Insomnia

13.3

Anxiety

Initial insomnia

Depressed mood

Restlessness

Agitation

Nervousness

Bruxism

Depression

Affect lability

Libido decreased*

Panic attack

Tension

Aggression

Confusional state

Nervous System Disorders

Headache

24.2

18.8

Dizziness

Tremor

Paraesthesia

Tension headache

Eye Disorders

Accommodation disorder

Vision blurred

Ear and Labyrinth Disorders

Vertigo

Cardiac Disorders

Tachycardia

Palpitations

Vascular Disorders

Hypertension

Hot flush

Respiratory, Thoracic and Mediastinal Disorders

Oropharyngeal pain

Cough

Dyspnoea

Gastrointestinal Disorders

Dry mouth

15.1

Nausea

14.3

Dyspepsia

Vomiting

Constipation

Skin and Subcutaneous Tissue Disorders

Hyperhidrosis

Musculoskeletal and Connective Tissue Disorders

Muscle tightness

Muscle spasms

Reproductive System and Breast Disorders

Erectile dysfunction

General Disorders and Administration Site Conditions

Irritability

Fatigue

Thirst

CCDS181023

Page 12 of 18

CONCERTA(181127)ADS

System/Organ Class

Adverse Drug Reaction

CONCERTA

(n=596)

%

Placebo

(n=309)

%

Asthenia

Investigations

Weight decreased

Heart rate increased

Blood pressure increased

Alanine aminotransferase increased

*The adverse reaction libido decreased includes the preferred term loss of libido

The majority of ADRs were mild to moderate in severity.

Open-Label Data – Adverse Drug Reactions Reported at

1% Frequency

The safety of CONCERTA was evaluated in 3782 paediatric and adult subjects with ADHD who participated

in 12 open-label clinical trials. The information presented in this section was derived from pooled data.

Adverse Drug Reactions (ADRs) reported by

1% of CONCERTA-treated subjects in these trials and not listed

Table 2

Table 3

are shown in

Table 4.

Table 4. Adverse Drug Reactions Reported by

1% of CONCERTA-Treated Subjects in

12 Open-Label Clinical Trials

System/Organ Class

Adverse Drug Reaction

CONCERTA

(n=3782)

%

Psychiatric Disorders

Mood swings

Nervous System Disorders

Somnolence

Gastrointestinal Disorders

Diarrhea

Abdominal discomfort

Abdominal pain

Skin and Subcutaneous Tissue Disorders

Rash

General Disorders and Administration Site Conditions

Feeling jittery

The majority of ADRs were mild to moderate in severity.

Double Blind and Open-Label Data – Adverse Drug Reactions Reported at <1% Frequency

Additional ADRs that occurred in <1% of CONCERTA-treated paediatric and adult subjects in the double-blind

and open-label clinical datasets are listed in

Table 5

Table 5. Adverse Drug Reactions Reported by <1% of CONCERTA-Treated Pediatric and

Adult Subjects in Either Double-Blind or Open-Label Clinical Trials

Blood and Lymphatic System Disorders

Leukopenia

Psychiatric Disorders

Anger, Sleep disorder, Hypervigilance, Tearfulness, Mood altered

Nervous System Disorders

Psychomotor hyperactivity, Sedation, Lethargy

CCDS181023

Page 13 of 18

CONCERTA(181127)ADS

Eye Disorders

Dry eye

Skin and Subcutaneous Tissue Disorders

Rash macular

Investigations

Cardiac murmur

The majority of ADRs were mild to moderate in severity.

Postmarketing Data

ADRs identified during postmarketing experience with CONCERTA are included in

Table 6

. The frequencies

are provided according to the following convention:

Very common

1/10

Common

1/100 and <1/10

Uncommon

1/1000 and <1/100

Rare

1/10000 and <1/1000

Very rare

<1/10000, including isolated reports

Table 6. Adverse Drug Reactions Identified During Postmarketing Experience with CONCERTA

by Frequency Category Estimated from Spontaneous Reporting Rates

Blood and Lymphatic System Disorders

Very rare

Pancytopenia, Thrombocytopenia, Thrombocytopenic, Purpura

Immune System Disorders

Rare

Hypersensitivity reactions such as Angioedema, Anaphylactic reactions, Auricular

swelling, Bullous conditions, Exfoliative conditions, Urticarias, Pruritus NEC,

Rashes, Eruptions and Exanthemas NEC

Psychiatric Disorders

Very rare

Disorientation, Hallucination, Hallucination Auditory, Hallucination Visual,

Mania, Logorrhoea, libido disorder*

Nervous System Disorders

Very rare

Convulsion, Grand Mal Convulsion, Dyskinesia, Cerebrovascular disorder

(including cerebral vasculitis, cerebral haemorrhage, cerebral arteritis, cerebral

vascular occlusion)

Eye Disorders

Very rare

Diplopia, Mydriasis, Visual Impairment

Cardiac Disorders

Very rare

Angina Pectoris, Bradycardia, Extrasystoles, Supraventricular Tachycardia,

Ventricular Extrasystoles

Vascular Disorders

Very rare

Raynaud’s Phenomenon

Skin and Subcutaneous Tissue Disorders

Very rare

Alopecia, Erythema

Hepatobiliary Disorders

Very rare

Hepatocellular injury, Acute hepatic failure

Musculoskeletal, and Connective Tissue Disorders

Very rare

Arthralgia, Myalgia, Muscle Twitching

Reproductive System and Breast Disorders

Very rare

Priapism

General Disorders and Administration Site Conditions

Rare

Therapeutic Response Decreased

Very rare

Chest Pain, Chest Discomfort, Drug Effect Decreased, Hyperpyrexia

Investigations

CCDS181023

Page 14 of 18

CONCERTA(181127)ADS

Very rare

Blood Alkaline Phosphatase Increased, Blood Bilirubin Increased, Hepatic Enzyme

Increased, Platelet Count Decreased, White Blood Cell Count Abnormal

NEC = not elsewhere classified

*The adverse reaction libido disorder includes terms apart from those associated with decreases in libido

4.9.

Overdose

The prolonged release of methylphenidate from CONCERTA should be considered when treating patients with

overdose.

Signs and Symptoms

Signs and symptoms of CONCERTA overdosage, resulting principally from overstimulation of the CNS and

from excessive sympathomimetic effects, may include the following: vomiting, agitation, muscle twitching,

convulsion, grand mal convulsion, confusional state, hallucination (auditory and/or visual), hyperhidrosis,

headache, pyrexia, tachycardia, palpitations, heart rate increased, sinus arrhythmia, hypertension, mydriasis, and

dry mouth.

Treatment

Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and

against external stimuli that would aggravate overstimulation already present. The efficacy of activated charcoal

has not been established. Intensive care must be provided to maintain adequate circulation and respiratory

exchange; external cooling procedures may be required for pyrexia.

Efficacy of peritoneal dialysis or extracorporeal haemodialysis for CONCERTA overdosage has not been

established.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties

Pharmacotherapeutic group: centrally acting sympathomimetics: ACT code: N06BA04

Methylphenidate is a central nervous system stimulant. The mode of therapeutic action in Attention Deficit

Hyperactivity

Disorder

(ADHD)

known.

Methylphenidate

thought

block

reuptake

noradrenaline and dopamine into the presynaptic neuron and increase the release of these monoamines into the

extraneuronal space.

Methylphenidate

hydrochloride

racemic

mixture

methyl

-phenyl-2-piperidineacetate

hydrochloride. The d-isomer is pharmacologically more active than the l-isomer.

Clinical Trials

Children

CONCERTA was demonstrated to be effective in the treatment of ADHD, in children aged 6 to 12 years, in

three pivotal studies. Studies 1 and 2 were single-centre, double-blind, double-dummy, randomised, placebo

and active-controlled, crossover comparisons (n = 64 and 70). Study 3 was a multicentre, 4 week, double-blind,

double-dummy, randomised, placebo and active-controlled, parallel study (n = 282). The primary comparison

of interest in all three trials was CONCERTA versus placebo.

The primary efficacy parameter for CONCERTA was the Inattention/Overactivity with Aggression (IOWA)

Conners I/O subscale rated by the community school teacher. Statistically significant (p < 0.001) reduction in

the Inattention/Overactivity subscale versus placebo was shown consistently across all three controlled studies

for CONCERTA once daily.

Onset and duration of efficacy were assessed by the laboratory school teacher using the SKAMP (Swanson,

Kotkin, Agler, M-Fynn and Pelham) combined attention ratings for studies 1 and 2. The onset of efficacy was

CCDS181023

Page 15 of 18

CONCERTA(181127)ADS

estimated to be 1.5 hours and duration continued through to 12 hours. Patients demonstrated higher productivity

and greater accuracy during CONCERTA treatment.

Adults

Two double-blind, placebo-controlled studies were conducted in 627 adults aged 18 to 65 years. The controlled

studies compared CONCERTA administered once daily and placebo in a multi-centre, parallel group, 5-week,

fixed-dose study (Study 4) (18, 36, and 72 mg/day) and in a multi-centre, parallel group, 7-week dose-titration

study (Study 5) (36 to 108 mg/day).

Study 4 was a multi-centre, double-blind, randomized, placebo-controlled, parallel group, dose-response study

(5-week duration) with 3 fixed dose groups (18, 36, and 72 mg). Patients were randomized to receive

CONCERTA administered at doses of 18 mg (n=101), 36 mg (n=102), 72 mg/day (n=102), or placebo (n=96).

All three doses of CONCERTA were significantly more effective than placebo in improving CAARS (Conners’

Adult ADHD Rating Scale) total scores at double-blind end point in adult subjects with ADHD.

Study 5 demonstrated the effectiveness of CONCERTA in the treatment of ADHD in adults aged 18 to 65 years

at doses from 36 mg/day to 108 mg/day based on the change from baseline to final study visit on the Adult

ADHD Investigator Rating Scale (AISRS). Of 226 patients who entered the 7-week trial, 110 were randomized

to CONCERTA and 116 were randomized to placebo. Treatment was initiated at 36 mg/day and patients

continued with incremental increases of 18 mg/day (36 to 108 mg/day) based on meeting specific improvement

criteria with acceptable tolerability. At the final study visit, mean change scores (LS Mean, SEM) for the

investigator rating on the AISRS demonstrated that CONCERTA was significantly superior to placebo.

5.2.

Pharmacokinetic properties

Absorption

Methylphenidate is readily absorbed. Following oral administration of CONCERTA to adults, the drug overcoat

dissolves and plasma methylphenidate concentrations increase rapidly reaching an initial maximum at about 1

to 2 hours. The methylphenidate contained in two internal drug layers is gradually released over the next few

hours.

Peak

plasma

concentrations

achieved

about

hours

after

which

plasma

levels

methylphenidate gradually decrease. CONCERTA once daily minimises the fluctuations between peak and

trough concentrations associated with immediate-release methylphenidate three times daily. The extent of

absorption of CONCERTA once daily is generally comparable to conventional immediate release preparations

given three times daily.

Following the administration of CONCERTA 18 mg once daily in 36 adults, the mean pharmacokinetic

parameters were C

3.7 ± 1.0 ng/mL, T

6.8 ± 1.8 h, AUC

41.8 ± 13.9 ngh/mL and t

3.5 ± 0.4 h. No

differences in the pharmacokinetics of CONCERTA were noted following single and repeated once daily dosing

indicating no significant drug accumulation. The AUC and t

following repeated once daily dosing are similar

to those following the first dose of CONCERTA 18 mg.

Following administration of CONCERTA in single doses of 18, 36 and 54 mg/day to adults, C

and AUC

of d-methylphenidate were proportional to dose, whereas l-methylphenidate C

and AUC

increased

disproportionately with respect to dose. Following administration of CONCERTA, plasma concentrations of the

l-isomer were approximately 1/40th the plasma concentrations of the d-isomer.

In healthy adults, single and multiple dosing of once daily CONCERTA doses from 54 to 144 mg/day resulted

in linear and dose proportional increases in C

and AUC

for total methylphenidate (MPH) and its major

metabolite, (alpha)-phenyl-piperidine acetic acid (PPAA). The single dose and steady state (Day 4) clearance

and half-life parameters were similar, indicating that there was no time dependency in the pharmacokinetics of

methylphenidate. The ratio of metabolite (PPAA) to parent drug (MPH) was constant across doses from 54 to

144 mg/day, both after single dose and upon multiple dosing.

Pharmacokinetic equivalence has been demonstrated for two 27-mg CONCERTA tablets with three 18-mg

CONCERTA tablets. The mean values of the treatment ratio (2 x 27 mg fasted/3 x 18 mg fasted) of the log-

transformed pharmacokinetic values for C

and AUC

were 101.1%, 104.3% and 100.3% respectively.

The 90% CIs for the treatment ratios were within the pre-specified 80% - 125% range.

CCDS181023

Page 16 of 18

CONCERTA(181127)ADS

In a multiple dose study in adolescent ADHD patients aged 13 to 16 administered their prescribed dose (18 to

72 mg/day) of CONCERTA, mean C

and AUC

of methylphenidate increased proportionally with respect

to dose.

Studies on the effects of dosing after overnight fasting, after consumption of a normal breakfast and a high-fat

breakfast showed no differences in pharmacokinetics or pharmacodynamics of CONCERTA. There is no

evidence of dose dumping in the presence or absence of food.

Distribution

Plasma methylphenidate concentrations in adults decline biexponentially following oral administration. The

terminal plasma half-life of methylphenidate in adults following oral administration of CONCERTA was

approximately 3.5 hours.

Metabolism

In humans, methylphenidate is metabolised primarily by de-esterification to

-phenyl-piperidine acetic acid

(PPAA) which has little or no pharmacologic activity. In adults the metabolism of CONCERTA once daily, as

evaluated by metabolism to PPAA, is similar to that of methylphenidate three times daily. The metabolism of

single and repeated once daily doses of CONCERTA is similar.

Elimination

After oral dosing of radiolabelled methylphenidate in humans, about 90% of the radioactivity was recovered in

urine. The main urinary metabolite was PPAA, accounting for approximately 80% of the dose. Since renal

clearance is not an important route of methylphenidate clearance, renal insufficiency is not expected to have a

significant effect on the pharmacokinetics of CONCERTA.

5.3.

Preclinical safety data

Carcinogenicity

In a lifetime dietary carcinogenicity study carried out in mice, methylphenidate caused an increase in

hepatocellular adenomas at a dose of 60–80 mg/kg/day, and in males only, an increase in hepatoblastomas (a

relatively rare rodent malignant tumour type) at 60 mg/kg/day. These dose levels are approximately 3–8 fold

maximal

recommended

clinical

dose

mg/m

basis.

There

increase

tumours

30-40 mg/kg/day (approximately 1-4 fold the maximal recommended clinical dose on a mg/m

basis). The

mouse strain used is sensitive to the development of hepatic tumours, and the significance of these results to

humans is not known. There was no evidence of carcinogenicity in two strains of transgenic mice administered

methylphenidate in the diet for 24 weeks at doses up to 60–74 mg/kg/day (approximately 3–8 fold the maximal

recommended clinical dose on a mg/m

basis) or in a lifetime dietary study in rats at doses up to 50 mg/kg/day

(approximately 4–10 fold the maximal recommended clinical dose on a mg/m

basis).

Mutagenicity

Methylphenidate was not mutagenic in the

in vitro

assays (Ames reverse mutation assay, mouse lymphoma cell

forward mutation assay). Methylphenidate was weakly clastogenic

in vitro

(Chinese Hamster ovary cells) but

was negative

in vivo

(mouse bone marrow micronucleus assay). Sister chromatid exchange assay results were

positive only at high (cytotoxic) concentrations.

Impairment of fertility

Dietary administration of methylphenidate to male and female mice at doses up to 150–160 mg/kg/day did not

impair fertility in an 18–week continuous breeding study in which both parents and offspring were treated. This

dose was approximately 7–16 fold the maximal recommended human dose on a mg/m

basis.

6.

PHARMACEUTICAL PARTICULARS

CCDS181023

Page 17 of 18

CONCERTA(181127)ADS

6.1.

List of excipients

Butylated hydroxytoluene

Carnauba wax

Cellulose acetate

Hypromellose

Lactose

Opacode black NS-78-17715

Opadry clear YS-1-19025-A

Phosphoric acid

Poloxamer

Polyethylene oxide

Povidone

Sodium chloride

Stearic acid

Succinic acid

Synthetic iron oxides

The 18 mg tablet also contains Opadry II yellow YS-30-12788-A

The 27 mg tablet also contains Opadry II grey Y-30-17528

The 36 mg tablet also contains Opadry II white Y-30-18037

The 54 mg tablet also contains Opadry II red Y-30-15567-A

6.2.

Incompatibilities

Not applicable

6.3.

Shelf life

3 years

6.4.

Special precautions for storage

Store below 25°C. Keep container tightly closed.

6.5.

Nature and contents of container

CONCERTA tablets are supplied in HDPE bottles containing silica gel desiccant.

Pack sizes: 28, 30, 56, 60 and 100 tablets

Not all pack sizes may be marketed

6.6.

Special precautions for disposal and other handling

No special requirements

7.

MEDICINE SCHEDULE

Controlled Drug – B2

8.

SPONSOR

CCDS181023

Page 18 of 18

CONCERTA(181127)ADS

Janssen-Cilag (New Zealand) Ltd

Auckland, NEW ZEALAND

Telephone: 0800 800 806

9.

DATE OF FIRST APPROVAL

14 August 2003 (18 mg, 36 mg & 54 mg)

19 November 2007 (27 mg)

10.

DATE OF REVISION OF THE TEXT

27 November 2018

Summary table of changes:

Section changes

Summary of new information

1. Added pharmacodynamic interaction with antipsychotic drugs

2. Editorial changes

Similar products

Search alerts related to this product

Share this information