Maxalt 5mg tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Rizatriptan benzoate
Available from:
CST Pharma Ltd
ATC code:
N02CC04
INN (International Name):
Rizatriptan benzoate
Dosage:
5mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 04070401; GTIN: 5055946807171 5055946807188

PACKAGE LEAFLET: INFORMATION FOR THE USER

MAXALT

®

5mg tablets

(rizatriptan)

Read all of this leaflet carefully before you start taking this

medicine, because it contains important information for you.

The name of your medicine is Maxalt 5mg tablets, and will be referred

to as Maxalt throughout this leaflet. Maxalt Tablets are also available in

10mg strengths.

Keep this leaflet. You may need to read it again.

If you have further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to

others. It may harm them, even if their signs of illness are the same as

yours.

If you get any side effects talk to your doctor or pharmacist. This

includes any possible side effects not listed in this leaflet. See

section 4.

What is in this leaflet

1) What Maxalt is and what it is used for

2) What you need to know before you take Maxalt

3) How to take Maxalt

4) Possible side effects

5) How to store Maxalt

6) Contents of the pack and other information

1) WHAT MAXALT IS AND WHAT IT IS USED FOR

Maxalt belongs to a class of medicines called selective serotonin

5-HT

1B/1D

receptor agonists.

Maxalt is used to treat the headache phase of the migraine attack in

adults.

Treatment with Maxalt:

Reduces swelling of blood vessels surrounding the brain. This swelling

results in the headache pain of a migraine attack.

2) WHAT YOU NEED TO KNOW BEFORE YOU TAKE MAXALT

Do not take Maxalt if:

you are allergic to rizatriptan benzoate or any of the other ingredients

of this medicine (listed in section 6)

you have moderately severe or severe high blood pressure or mild

high blood pressure that is not controlled by medication

you have or have ever had heart problems including heart attack or

pain on the chest (angina) or you have experienced heart disease

related signs

you have severe liver or severe kidney problems

you have had a stroke (cerebrovascular accident CVA) or mini stroke

(transient ischaemic attack TIA)

you have blockage problems with your arteries (peripheral vascular

disease)

you are taking monoamine oxidase (MAO) inhibitors such as

moclobemide, phenelzine, tranylcypromine, or pargyline (drugs against

depression), or linezolid (an antibiotic), or if it has been less than two

weeks since you stopped taking MAO inhibitors

you are now taking ergotamine-type medications, such as ergotamine

or dihydro-ergotamine to treat your migraine or methysergide to

prevent a migraine attack

you are taking any other drug in the same class, such as sumatriptan,

naratriptan, or zolmitriptan to treat your migraine (see Other

medicines and Maxalt below).

If you are not sure if any of the above apply to you talk to your doctor or

pharmacist before taking Maxalt.

Warnings and precautions

Before you take Maxalt, tell your doctor or pharmacist, if:

you have any of the following risk factors for heart disease: high blood

pressure, diabetes, you smoke or you are using nicotine substitution,

your family has a history of heart disease, you are a man over 40

years of age, or you are a postmenopausal woman

you have kidney or liver problems

you have a particular problem with the way your heart beats (bundle

branch block)

you have or have had any allergies

your headache is associated with dizziness, difficulty in walking, lack of

co-ordination or weakness in the leg and arm

you use herbal preparation containing St. John's wort

you have had allergic reaction like swelling of face, lips, tongue and/or

throat which may cause difficulty breathing and/or swallowing

(angioedema)

you are taking selective serotonin reuptake inhibitors (SSRIs) such as

sertraline, escitalopram oxalate, and fluoxetine or serotonin

norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, and

duloxetine for depression

you have had short lived symptoms including chest pain and tightness.

If you take Maxalt too often this may result in you getting a chronic

headache. In such cases you should contact your doctor as you may

have to stop taking Maxalt.

Please tell your doctor or pharmacist about your symptoms. Your doctor

will decide if you have migraine. You should take Maxalt only for a

migraine attack. Maxalt should not be used to treat headaches that might

be caused by other, more serious conditions.

Please tell your doctor if you are taking or have recently taken, or plan to

take, any other medicines including medicines obtained without a

prescription. This includes herbal medicines and those you normally take

for a migraine. This is because Maxalt can affect the way some

medicines work. Also, other medicines can affect Maxalt.

Other medicines and Maxalt

Do not take Maxalt

if you are already taking a 5-HT

1B/1D

agonist (sometimes referred to as

‘triptans’), such as sumatriptan, naratriptan or zolmitriptan.

if you are taking a monoamine oxidase (MAO) inhibitor such as

moclobemide, phenelzine, tranylcypromine, linezolid, or pargyline or if

it has been less than two weeks since you stopped taking an MAO

inhibitor.

if you use ergotamine-type medications such as ergotamine or

dihydro-ergotamine to treat your migraine.

if you use methysergide to prevent a migraine attack.

The above listed medicines when taken with Maxalt may increase the

risk of side effects.

You should wait at least 6 hours after taking Maxalt before you take

ergotamine-type medications such as ergotamine or dihydro-ergotamine

or methysergide.

You should wait at least 24 hours after taking ergotamine-type

medications before taking Maxalt.

Ask your doctor for instructions and the risks about taking Maxalt

if you are taking propranolol (see section 3: How to take Maxalt).

if you are taking SSRIs such as sertraline, escitalopram oxalate, and

fluoxetine or SNRIs such as venlafaxine, and duloxetine for

depression.

Please tell your doctor or pharmacist if you are taking or have recently

taken any other medicines, including medicines obtained without a

prescription.

Maxalt with food and drink

Maxalt can take longer to work if it is taken after food. Although it is better

to take it on an empty stomach, you can still take it if you have eaten.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or

planning to have a baby, ask your doctor or pharmacist for advice before

taking this medicine.

It is not known whether Maxalt is harmful to an unborn baby when taken

by a pregnant woman. Breastfeeding should be avoided for 24 hours

after treatment.

Children and adolescents

The use of Maxalt tablets in children under 18 years of age is not

recommended.

Use in patients older than 65 years

There have been no full studies to look at how safe and effective Maxalt

is amongst patients older than 65 years.

Driving or using machines

You may feel sleepy or dizzy while taking Maxalt. If this happens, do not

drive or use any tools or machines.

Maxalt contains lactose monohydrate

The 5-mg tablet contains 30.25 mg of lactose monohydrate and the

10-mg tablet contains 60.50 mg of lactose monohydrate. If you have

been told by your doctor that you have an intolerance to some sugars,

contact your doctor before taking this medicinal product.

3) HOW TO TAKE MAXALT

Maxalt is used to treat migraine attacks. Take Maxalt as soon as

possible after your migraine headache has started. Do not use it to

prevent an attack.

Always take Maxalt exactly as your doctor has told you. You should

check with your doctor or your pharmacist if you are not sure.

The usual dose is 10 mg.

If you are currently taking propranolol or have kidney or liver problems

you should use the 5-mg dose of Maxalt. You should leave at least

2 hours between taking propranolol and Maxalt up to a maximum of 2

doses in a 24-hour period.

Maxalt (rizatriptan benzoate) tablets should be taken by mouth and

swallowed whole with liquid.

Maxalt is also available as a 10-mg oral lyophilisate that dissolves in the

mouth. The oral lyophilisate can be used in situations in which liquids are

not available, or to avoid the nausea and vomiting that may accompany

the ingestion of tablets with liquids.

If migraine returns within 24 hours

In some patients, migraine symptoms can return within a 24-hour period.

If your migraine does return you can take an additional dose of Maxalt.

You should always wait at least 2 hours between doses.

If after 2 hours you still have a migraine

If you do not respond to the first dose of Maxalt during an attack, you

should not take a second dose of Maxalt for treatment of the same

attack. It is still likely, however, that you will respond to Maxalt during the

next attack.

Do not take more than 2 doses of Maxalt in a 24-hour period, (for

example, do not take more than two 10-mg or 5-mg tablets or oral

lyophilisate in a 24-hour period). You should always wait at least 2

hours between doses.

If your condition worsens, seek medical attention.

If you take more Maxalt than you should:

If you take more Maxalt than you should, talk to your doctor or

pharmacist straight away. Take the medicine pack with you.

Signs of overdosage can include dizziness, drowsiness, vomiting, fainting

and slow heart rate.

If you have any further questions on the use of this product ask your

doctor or pharmacist.

4) POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not

everybody gets them. The following side effects may happen with this

medicine.

In adult studies, the most common side effects reported were dizziness,

sleepiness and tiredness.

Common (affects 1 to 10 users in 100)

tingling (paraesthesia), headache, decreased sensitivity of skin

(hypoaesthesia), decreased mental sharpness, insomnia.

fast or irregular heart beat (palpitation).

flushing (redness of the face lasting a short time).

throat discomfort.

feeling sick (nausea), dry mouth, vomiting, diarrhoea, indigestion

(dyspepsia).

feeling of heaviness in parts of the body, neck pain, stiffness.

pain in abdomen or chest.

Uncommon (affects 1 to 10 users in 1000)

bad taste in your mouth.

unsteadiness when walking (ataxia), dizziness (vertigo), blurred vision,

tremor, fainting (syncope).

confusion, nervousness.

high blood pressure (hypertension); thirst, hot flushes, sweating.

rash, itching and lumpy rash (hives); swelling of face, lips, tongue

and/or throat which may cause difficulty breathing and/or swallowing

(angioedema), difficulty breathing (dyspnoea).

feeling of tightness in parts of the body, muscle weakness.

changes in the rhythm or rate of the heartbeat (arrhythmia);

abnormalities of the electrocardiogram (a test that records the

electrical activity of your heart), very fast heartbeat (tachycardia).

facial pain, muscle pain.

Rare (affects 1 to 10 users in 10,000)

wheezing.

allergic reaction (hypersensitivity); sudden life-threatening allergic

reaction (anaphylaxis).

stroke (this generally occurs in patients with risk factors for heart and

blood vessel disease (high blood pressure, diabetes, smoking, use of

nicotine substitution, family history of heart disease or stroke, man

over 40 years of age, post-menopausal women, particular problem

with the way your heart beats [bundle branch block])).

slow heartbeat (bradycardia).

Not known (frequency cannot be estimated from the available data):

heart attack, spasm of the blood vessels of the heart (these generally

occur in patients with risk factors for heart and blood vessel disease

(high blood pressure, diabetes, smoking, use of nicotine substitution,

family history of heart disease or stroke, man over 40 years of age,

postmenopausal women, particular problem with the way your heart

beats (bundle branch block)).

a syndrome called “serotonin syndrome” that may cause side effects

like coma, unstable blood pressure, extremely high body temperature,

lack of muscle coordination, agitation, and hallucinations.

severe shedding of the skin with or without fever (toxic epidermal

necrolysis).

seizure (convulsions/fits).

spasm of blood vessels of the extremities including coldness and

numbness of the hands or feet.

spasm of the blood vessels of the colon (large bowel), which can

cause abdominal pain.

Tell your doctor right away if you have symptoms of allergic

reactions, serotonin syndrome, heart attack or stroke.

In addition, tell your doctor if you experience any symptoms that suggest

an allergic reaction (such as a rash or itching) after taking Maxalt.

Reporting of side effects

If you get any side effects, tell your doctor or pharmacist. This includes

any possible side effects not listed in this leaflet. You can also report side

effects directly via Yellow Card Scheme Website:

www.mhra.gov.uk/yellowcard.

By reporting side effects you can help provide more information on the

safety of this medicine.

5) HOW TO STORE MAXALT

Keep Maxalt out of the sight and reach of children.

Do not use Maxalt after the expiry date which is stated on the

container after EXP. The expiry date refers to the last day of the

month.

Do not store Maxalt above 30

If your tablets become discoloured or show any sign of deterioration,

return them to your pharmacist.

Medicines should not be disposed of via wastewater or household

waste. Ask your pharmacist how to dispose medicines no longer

required. These measures will help to protect the environment.

6) CONTENTS OF THE PACK AND OTHER INFORMATION

What Maxalt contains

The active substance of Maxalt is rizatriptan. Each tablet contains

7.265mg of rizatriptan benzoate, equivalent to 5mg rizatriptan.

The other ingredients of Maxalt tablets are lactose monohydrate,

microcrystalline cellulose, pregelatinised maize starch, red iron oxide

(E172) and magnesium stearate.

What Maxalt looks like and contents of pack

Maxalt 5mg tablets are pale pink, capsule-shaped tablets, coded ‘MSD’

on one side and ‘266’ on the other.

Maxalt is available in packs of 3 or 6 tablets.

Manufactured by Merck Sharp & Dohme BV, Waarderweg 39, 2031 BN,

Haarlem, The Netherlands. Procured from within the EU by the Product

Licence holder MPT Pharma Ltd, Westgate Business Park, Unit 5-7

Tintagel Way, Aldridge, Walsall WS9 8ER, U.K.

Repackaged by XXXXXXXXXXXXXXX

MAXALT 5mg tablets

PL: 33532/0254

How can you obtain more information about Maxalt?

This leaflet gives you some of the most important information about

Maxalt. If you have any questions after you have read it, ask your doctor

or pharmacist who can give you further information.

Further information about migraine is available from the following

organisations:

Migraine Action Association

Floor, 27 East Street

Leicester

LE1 6NB

Tel: 0116 275 8317

Fax: 0116 254 2023

The Migraine Trust

52-53 Russell Square

London

WC1B 4HP

Tel: 020 7631 6970

Fax: 020 7436 2886

Email: info@migrainetrust.org

(Migraine Action Association and The Migraine Trust are independent

organizations and are not associated with Merck Sharp & Dohme Limited

or MPT Pharma Limited.)

Maxalt

is a registered trademark of Merck & Co. Inc.

Leaflet dated 26

March 2015

Leaflet coded xxxxxxx

POM

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

MAXALT

5 mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 7.265 mg of rizatriptan benzoate (corresponding to 5 mg

of the rizatriptan).

Excipients with known effect: lactose monohydrate 30.25 mg in the 5 mg

tablet.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Tablet

5 mg tablets are pale pink, capsule-shaped, coded MSD on one side and 266

on the other.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Acute treatment of the headache phase of migraine attacks with or without

aura in adults.

4.2

Posology and method of administration

Method of administration

MAXALT should not be used prophylactically.

The oral tablets should be swallowed whole with liquid.

Effect of Food: The absorption of rizatriptan is delayed by approximately 1

hour when administered together with food. Therefore, onset of effect may be

delayed

when

rizatriptan

administered

state

(see

also

Pharmacokinetic properties, Absorption).

MAXALT is also available as an alternative oral lyophilisate.

Posology

Adults 18 years of age and older

The recommended dose is 10 mg.

Redosing: Doses should be separated by at least two hours; no more than two

doses should be taken in any 24-hour period.

for headache recurrence within 24 hours: If headache returns after relief

of the initial attack, one further dose may be taken. The above dosing

limits should be observed.

after non-response: The effectiveness of a second dose for treatment of

the same attack, when an initial dose is ineffective, has not been examined

in controlled trials. Therefore, if a patient does not respond to the first

dose, a second dose should not be taken for the same attack.

Clinical studies have shown that patients who do not respond to treatment of

an attack are still likely to respond to treatment for subsequent attacks.

Some

patients

should

receive

lower

dose

MAXALT,

particular the following patient groups:

patients on propranolol. Administration of rizatriptan should be separated

by at least two hours from administration of propranolol (see section 4.5).

patients with mild or moderate renal insufficiency.

patients with mild to moderate hepatic insufficiency.

Doses should be separated by at least two hours; no more than two doses

should be taken in any 24-hour period.

Paediatric population

Children and Adolescents (under 18 years of age)

The safety and efficacy of MAXALT in children and adolescents under 18

years of age has not yet been established.

Currently

available

data

described

sections

5.2,

recommendation on a posology can be made.

Older people

The safety and effectiveness of rizatriptan in patients older than 65 years have

not been systematically evaluated.

4.3

Contraindications

Hypersensitivity to rizatriptan or to any of the excipients listed in section 6.1.

Concurrent administration of monoamine oxidase (MAO) inhibitors or use

within two weeks of discontinuation of MAO inhibitor therapy. (see section

4.5).

MAXALT is contra-indicated in patients with severe hepatic or severe renal

insufficiency.

MAXALT is contra-indicated in patients with a previous cerebrovascular

accident (CVA) or transient ischaemic attack (TIA).

Moderately severe or severe hypertension or untreated mild hypertension.

Established coronary artery disease, including ischaemic heart disease (angina

pectoris, history of myocardial infarction, or documented silent ischaemia),

signs and symptoms of ischaemic heart disease, or Prinzmetal’s angina.

Peripheral vascular disease.

Concomitant use of rizatriptan and ergotamine, ergot derivatives (including

methysergide), or other 5-HT

1B/1D

receptor agonists. (See section 4.5).

4.4

Special warnings and precautions for use

MAXALT should only be administered to patients in whom a clear diagnosis

of migraine has been established. MAXALT should not be administered to

patients with basilar or hemiplegic migraine.

MAXALT should not be used to treat ‘atypical’ headaches, i.e. those that

might be associated with potentially serious medical conditions, (e.g. CVA,

ruptured

aneurysm)

which

cerebrovascular

vasoconstriction

could

harmful.

Rizatriptan can be associated with transient symptoms including chest pain

and tightness which may be intense and involve the throat (see section 4.8).

Where such symptoms are thought to indicate ischaemic heart disease, no

further dose should be taken and appropriate evaluation should be carried out.

As with other 5-HT

1B/1D

receptor agonists, rizatriptan should not be given,

without prior evaluation, to patients in whom unrecognised cardiac disease is

likely or to patients at risk for coronary artery disease (CAD) [e.g. patients

with hypertension, diabetics, smokers or users of nicotine substitution therapy,

men over 40 years of age, post-menopausal women, patients with bundle

branch block, and those with strong family history for CAD]. Cardiac

evaluations may not identify every patient who has cardiac disease and, in

very rare cases, serious cardiac events have occurred in patients without

underlying

cardiovascular

disease

when

5-HT

agonists

have

been

administered. Those in whom CAD is established should not be given

MAXALT. (See section 4.3)

5-HT

1B/1D

receptor agonists have been associated with coronary vasospasm. In

rare cases, myocardial ischaemia or infarction have been reported with 5-

1B/1D

receptor agonists including MAXALT (see section 4.8)

Other 5-HT

1B/1D

agonists, (e.g. sumatriptan) should not be used concomitantly

with MAXALT. (See section 4.5).

It is advised to wait at least six hours following use of rizatriptan before

administering

ergotamine-type

medications,

(e.g.

ergotamine,

dihydro-

ergotamine or methysergide). At least 24 hours should elapse after the

administration of an ergotamine-containing preparation before rizatriptan is

given. Although additive vasospastic effects were not observed in a clinical

pharmacology study in which 16 healthy males received oral rizatriptan and

parenteral ergotamine, such additive effects are theoretically possible, (see

section 4.3)

Serotonin syndrome (including altered mental status, autonomic instability and

neuromuscular abnormalities) has been reported following concomitant

treatment with triptans and selective serotonin reuptake inhibitors (SSRIs) or

serotonin noradrenaline reuptake inhibitors (SNRIs). These reactions can be

severe. If concomitant treatment with rizatriptan and an SSRI or SNRI is

clinically warranted, appropriate observation of the patient is advised,

particularly during treatment initiation, with dose increases, or with addition of

another serotonergic medication (see section 4.5).

Undesirable effects may be more common during concomitant use of triptans

(5-HT

1B/1D

agonists)

herbal

preparations

containing

John’s

wort

(Hypericum perforatum).

Angioedema (e.g. facial oedema, tongue swelling and pharyngeal oedema)

may occur in patients treated with triptans, among which rizatriptan. If

angioedema of the tongue or pharynx occurs, the patient should be placed

under medical supervision until symptoms have resolved. Treatment should

promptly be discontinued and replaced by an agent belonging to another class

of drugs.

The quantity of lactose monohydrate in each tablet is as follows: 30.25 mg in

the 5 mg tablet and 60.50 mg in the 10 mg tablet. Patients with rare hereditary

problems of galactose intolerance, the Lapp lactase deficiency or glucose-

galactose malabsorption should not take this medicine.

potential

interaction

should

considered

when

rizatriptan

administered to patients taking CYP 2D6 substrates (see section 4.5)

Medication overuse headache (MOH)

Prolonged use of any painkiller for headaches can make them worse. If this

situation is experienced or suspected, medical advice should be obtained and

treatment should be discontinued. The diagnosis of MOH should be suspected

in patients who have frequent or daily headaches despite (or because of) the

regular use of headache medications.

4.5

Interaction with other medicinal products and other forms of interaction

Ergotamine, ergot derivatives

(including methysergide), other 5 HT

1B/1D

receptor agonists: Due to an additive effect, the concomitant use of rizatriptan

and ergotamine, ergot derivatives (including methysergide), or other 5 HT

1B/1D

receptor agonists (e.g. sumatriptan, zolmitriptan, naratriptan) increase the

risk

coronary

artery

vasoconstriction

hypertensive

effects.

This

combination is contraindicated (see section 4.3).

Monoamine oxidase inhibitors: Rizatriptan is principally metabolised via

monoamine

oxidase,

‘A’

subtype

(MAO-A).

Plasma

concentrations

rizatriptan and its active N-monodesmethyl metabolite were increased by

concomitant

administration

selective,

reversible

MAO-A

inhibitor.

Similar or greater effects are expected with non-selective, reversible (e.g.

linezolid) and irreversible MAO inhibitors. Due to a risk of coronary artery

vasoconstriction and hypertensive episodes, administration of MAXALT to

patients taking inhibitors of MAO is contraindicated (see section 4.3).

Beta-Blockers:

Plasma

concentrations

rizatriptan

increased

concomitant administration of propranolol. This increase is most probably due

to first-pass metabolic interaction between the two drugs, since MAO-A plays

a role in the metabolism of both rizatriptan and propranolol. This interaction

leads to a mean increase in AUC and C

of 70-80%. In patients receiving

propranolol, the 5 mg dose of MAXALT should be used (see section 4.2).

In a drug interaction study, nadolol and metoprolol did not alter plasma

concentrations of rizatriptan.

Selective Serotonin Reuptake Inhibitors (SSRIs) /Serotonin Norepinephrine

Reuptake Inhibitors (SNRIs) and Serotonin Syndrome: There have been reports

describing

patients

with

symptoms

compatible

with

serotonin

syndrome

(including altered mental status, autonomic instability

and neuromuscular

abnormalities) following the use of selective serotonin reuptake inhibitors

(SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans

(see section 4.4).

In vitro studies indicate that rizatriptan inhibits cytochrome P450 2D6 (CYP

2D6). Clinical interaction data are not available. The potential for interaction

should be considered when rizatriptan is administered to patients taking CYP

2D6 substrates.

4.6

Fertility, pregnancy and lactation

Fertility

Effects on human fertility have not been investigated. Animal studies only

revealed minimal effects on fertility at plasma concentrations far in excess of

human therapeutic concentrations (more than 500-fold).

Pregnancy

The safety of rizatriptan for use in human pregnancy has not been established.

Animal studies do not indicate harmful effects at dose levels that exceed

therapeutic dose levels with respect to the development of the embryo or

foetus, or the course of gestation, parturition and post-natal development.

Because

animal

reproductive

developmental

studies

always

predictive of human response, MAXALT should be used during pregnancy

only if clearly needed.

Breast-feeding

Studies in rats indicated very high milk transfer of rizatriptan occurred.

Transient,

very

slight

decreases

pre-weaning

body

weights

were

observed only when the mother’s systemic exposure was well in excess of the

maximum exposure levels for humans. No data exist in humans.

Therefore, caution should be exercised when administering rizatriptan to

women who are breast-feeding. Infant exposure should be minimised by

avoiding breast-feeding for 24 hours after treatment.

4.7

Effects on Ability to Drive and Use Machines

Migraine or treatment with ‘Maxalt’ may cause somnolence in some patients.

Dizziness has also been reported in some patients receiving ‘Maxalt’. Patients

should, therefore, evaluate their ability to perform complex tasks during

migraine attacks and after administration of ‘Maxalt’.

4.8

Undesirable effects

MAXALT (as the tablet and oral lyophilisate formulation) was evaluated in

8630 adult patients for up to one year in controlled clinical studies. The most

common side effects evaluated in clinical studies were dizziness, somnolence,

and asthenia/fatigue. The following side effects have been evaluated in clinical

studies and/or reported in post-marketing experience:

(Very common [

1/10]; Common [

1/100, <1/10]; Uncommon [

1/1000,

<1/100]; Rare [

1/10,000 <1/1,000]; Very rare [

1/10000], not known

[cannot be estimated from the available data]).

Immune system disorders:

Rare: hypersensitivity reaction, anaphylaxis/anaphylactoid reaction.

Pyschiatric disorders:

Common: insomnia

Uncommon: disorientation, nervousness.

Nervous system disorders:

Common:

dizziness,

somnolence,

paraesthesia,

headache,

hypoaesthesia,

decreased mental acuity.

Uncommon: ataxia, vertigo, dysgeusia/bad taste, tremor, syncope

Not known: seizure, serotonin syndrome.

Eye disorders:

Uncommon: blurred vision.

Cardiac disorders:

Common: palpitation.

Uncommon: arrhythmia, ECG abnormalities, tachycardia

Rare: cerebrovascular accident (most of these adverse reactions have been

reported in patients with risk factors predictive of coronary artery disease),

bradycardia

Not

known:

myocardial

ischaemia

infarction

(most

these

adverse

reactions

have

been

reported

patients

with

risk

factors

predictive

coronary artery disease)

Vascular disorders:

Uncommon: hypertension, hot flushes/flashes

Not known: peripheral vascular ischaemia.

Respiratory, thoracic and mediastinal disorders:

Common: pharyngeal discomfort

Uncommon: dyspnoea

Rare: wheezing.

Gastro-intestinal disorders:

Common: nausea, dry mouth, vomiting, diarrhoea, dyspepsia

Uncommon: thirst,

Not known: ischemic colitis.

Skin and subcutaneous tissue disorders:

Common: flushing.

Uncommon:

pruritus,

urticaria,

angioedema

(e.g.

facial

oedema,

tongue

swelling, pharyngeal oedema) (for angioedema see also section 4.4), rash,

sweating

Not known: toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders:

Common: regional heaviness, neck pain, stiffness

Uncommon: regional tightness, muscle weakness, facial pain, myalgia.

General disorders and administration site conditions:

Common: asthenia/fatigue, pain in abdomen or chest.

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

Rizatriptan 40 mg (administered as either a single dose or as two doses with a

two-hour interdose interval) was generally well tolerated in over 300 adult

patients;

dizziness

somnolence

were

most

common

drug-related

adverse effects.

clinical

pharmacology

study

which

adult

subjects

received

rizatriptan, at total cumulative doses of 80 mg (given within four hours), two

subjects experienced syncope and/or bradycardia. One subject, a female aged

29 years, developed vomiting, bradycardia, and dizziness beginning three

hours after receiving a total of 80 mg rizatriptan (administered over two

hours). A third degree AV block, responsive to atropine, was observed an

hour after the onset of the other symptoms. The second subject, a 25 year old

male,

experienced

transient

dizziness,

syncope,

incontinence,

five-

second

systolic

pause

monitor)

immediately

after

painful

venipuncture. The venipuncture occurred two hours after the subject had

received a total of 80 mg rizatriptan (administered over four hours).

In addition, based on the pharmacology of rizatriptan, hypertension or other

more serious cardiovascular symptoms could occur after overdosage. Gastro-

intestinal decontamination, (e.g. gastric lavage followed by activated charcoal)

should be considered in patients suspected of an overdose with MAXALT.

Clinical and electrocardiographic monitoring should be continued for at least

12 hours, even if clinical symptoms are not observed.

The effects of haemo- or peritoneal dialysis on serum concentrations of

rizatriptan are unknown.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic

group:

antimigraine

preparations,

selective

serotonin

(5HT1) agonist, ATC-code: N02C C04.

Mechanism of action: Selective Serotonin (5-HT

1B/1D

) agonists

Rizatriptan binds selectively with high affinity to human 5-HT

and 5-HT

receptors and has little or no effect or pharmacological activity at 5-HT

5-HT

adrenergic alpha

, alpha

or beta; D

, dopaminergic, histaminic H

muscarinic; or benzodiazepine receptors.

The therapeutic activity of rizatriptan in treating migraine headache may be

attributed

agonist

effects

5-HT

5-HT

receptors

extracerebral intracranial blood vessels that are thought to become dilated

during an attack and on the trigeminal sensory nerves that innervate them.

Activation of these 5-HT

and 5-HT

receptors may result in constriction of

pain

producing

intracranial

blood

vessels

inhibition

neuropeptide

release that leads to decreased inflammation in sensitive tissues and reduced

central trigeminal pain signal transmission.

Pharmacodynamic effects

Adults

The efficacy of MAXALT Tablets in the acute treatment of migraine attacks

was established in four multicentre, placebo-controlled trials that included

over 2,000 patients who received MAXALT 5 or 10 mg for up to one year.

Headache

relief

occurred

early

minutes

following

dosing,

response rates (i.e. reduction of moderate or severe headache pain to no or

mild pain) two hours after treatment were 67-77% with the 10-mg tablet,

60-63% with the 5-mg tablet, and 23-40% with placebo. Although patients

who did not respond to initial treatment with MAXALT were not redosed for

the same attack, they were still likely to respond to treatment for a subsequent

attack. MAXALT reduced the functional disability and relieved the nausea,

photophobia, and phonophobia associated with migraine attacks.

MAXALT remains effective in treating menstrual migraine, i.e. migraine that

occurs within 3 days before or after the onset of menses.

Paediatric population

The European Medicines Agency has waived the obligation to submit the

results of studies with MAXALT tablets in all subsets of the paediatric

population in the treatment of migraine. See section 4.2 for information on

paediatric use.

Adolescents (12-17 years of age)

The efficacy of MAXALT oral lyophilisates in paediatric patients (12 to

17 years of age) was evaluated in a multicenter, randomized, double-blind,

placebo-controlled, parallel group study (n=570). The patient population was

required to be historically non-responsive to NSAIDs and acetaminophen

therapy. Patients with a qualifying migraine headache initially administered

placebo or rizatriptan within 30 minutes of onset. Following the 15 minute

placebo run-in, subjects who did not respond to placebo then treated a single

migraine attack with placebo or rizatriptan. Using a weight-based dosing

strategy, patients 20 kg to <40 kg received 5mg rizatriptan and patients

40 kg

received 10mg rizatriptan.

In this enriched population study, a difference of 9% between active treatment

and placebo was observed for the primary efficacy endpoint of pain freedom

(reduction from moderate or severe pain to no pain) 2 hours after treatment

(31%

under

rizatriptan

placebo

(p=0.025)).

significant

difference for the secondary endpoint of pain relief (reduction from moderate

or severe pain to mild or no pain) was found.

Children (6-11 years of age)

The efficacy of MAXALT oral lyophilisates was also evaluated in paediatric

patients 6 to 11 years of age in the same acute placebo-controlled clinical trial

(n=200). The percentage of patients achieving pain freedom 2 hours after

treatment was not statistically significantly different in patients who received

MAXALT oral lyophilisates 5 and 10 mg, compared with those who received

placebo (39.8% vs. 30.4%, p=0.269).

5.2

Pharmacokinetic properties

Absorption

Rizatriptan is rapidly and completely absorbed following oral administration.

The mean oral bioavailability of the tablet is approximately 40-45%, and mean

peak plasma concentrations (C

) are reached in approximately 1-1.5 hours

). Administration of an oral tablet dose with a high-fat breakfast had no

effect on the extent of rizatriptan absorption, but absorption was delayed for

approximately one hour.

Effect of Food: The effect of food on the absorption of rizatriptan from the oral

lyophilisate has not been studied. For the rizatriptan tablets, T

is delayed by

approximately 1 hour when the tablets are administered in the fed state. A

further

delay

absorption

rizatriptan

occur

when

oral

lyophilisate is administered after meals (see section 4.2).

Distribution

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