Consumer medicine information

What is in this leaflet

Read this leaflet carefully before taking your medicine.

This leaflet answers some common questions about Rizatriptan Orally Disintegrating Tablets. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

• if there is anything you do not understand in this leaflet,
• if you are worried about taking your medicine, or
• to obtain the most up-to-date information.

You can also download the most up to date leaflet from www.apotex.com.au.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

Keep this leaflet with your medicine. You may want to read it again.

What this medicine is used for

The name of your medicine is APO-Rizatriptan Orally Disintegrating Tablets. It contains the active ingredient rizatriptan benzoate.

It is used to relieve the headache pain and other symptoms of migraine attacks.

Rizatriptan Orally Disintegrating Tablets do not work for other types of headaches.

Migraine is an intense, throbbing, typically one-sided headache. It often includes nausea, vomiting, sensitivity to light, and sensitivity to sound. Some people may have visual symptoms before the headache, called an aura. An aura can include flashing lights or wavy lines.

Migraine attacks last anything from two hours to two days and they can return frequently. The severity and frequency of migraine attacks may vary.

Migraine occurs in about one out every 10 people. It is three times more common in women than men.

Six out of ten migraine sufferers their first attack before the age of 20.

There is no single cause of migraine.

It tends to run in families. Certain things, singly or in combination, trigger migraine attacks in some people. Some of these triggers are:

• Certain foods or drinks, for example, cheese and other dairy products, chocolate, citrus fruit, caffeine, alcohol (especially red wine)
• Stress, anger, worry
• Changes in routine, for example, under or over sleeping, missing meal, change in diet
• Bright light or loud noises
• Hormonal changes in women, example, during menstrual periods

If you understand what triggers your attacks, you may be able to prevent migraine attacks or reduce their frequency. Keeping a headache diary will help you identify and monitor of the possible migraine triggers encounter. Once the triggers are identified, you and your doctor can modify your treatment and lifestyle appropriately.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

How it works

During a migraine attack, blood vessels in the brain dilate, or widen, resulting in a throbbing pain.

Rizatriptan decreases this widening, returning the blood vessels to their normal size, and therefore helps to relieve the pain. Rizatriptan also blocks the release of certain chemicals from nerve endings that cause more pain and other symptoms of migraine.

There is no evidence that this medicine is addictive

Use in children

This medicine should not be used in children.

The safety and effectiveness of rizatriptan in children under 18 years have not been established.

Before you take this medicine

When you must not take it

Do not take this medicine if:

• You have or have had any of the following:
• Concurrent administration of monoamine oxidase inhibitors (MAOIs) for depression, or use within 2 weeks of discontinuation of MAOIs therapy. MAOIs include moclobemide, phenelzine, tranylcypromine and pargyline.
• Uncontrolled hypertension
• Established coronary artery disease, including ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), signs and symptoms of ischemic heart disease, or Prinzmetal's angina
• History of stroke or transient ischemic attack (TIA)
• Peripheral vascular disease, including (but not limited to) ischemic bowel disease
• You are hypersensitive to, or have had an allergic reaction to, rizatriptan or any of the ingredients listed at the end of this leaflet.
  Symptoms of an allergic reaction may include: cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin; fainting; or hay fever-like symptoms.
  If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.
• The expiry date (EXP) printed on the pack has passed.
• The packaging is torn, shows signs of tampering or it does not look quite right.
• If you are not sure whether you should start taking rizatriptan, talk to your doctor.
• Do not give rizatriptan to children under 18 years of age.

Before you start to take it

Before you start taking this medicine, tell your doctor if:

1. You have allergies to:

• any other medicines
• any other substances, such as foods, preservatives or dyes.

2. You have or have had any medical conditions, especially the following:
3. You are currently pregnant or you plan to become pregnant. Do not take this medicine whilst pregnant.
   Like most medicines, rizatriptan is not recommended for use during pregnancy. If there is need to consider rizatriptan during pregnancy, your doctor will discuss with you the risks and benefits of taking them during pregnancy
4. You are currently breastfeeding or you plan to breast-feed. Do not take this medicine whilst breastfeeding.
   It is not known whether rizatriptan pass into breast milk. Your doctor will discuss with you the risks and benefits of taking them while breast-feeding.
5. You have any risks factors for heart or blood vessel disease, including:

• high blood pressure
• diabetes
• smoking
• a high cholesterol level
• a family history of heart or blood vessel disease

6. Your headache is more severe than your 'usual' migraine, or it behaves differently
7. You have, or have had, any other medical conditions
8. You are planning to have surgery or an anaesthetic.
9. You are currently receiving or are planning to receive dental treatment.
10. You are taking or are planning to take any other medicines. This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

Some medicines should not be taken with rizatriptan. These include:

• monoamine oxidase inhibitors (MAOIs) used to treat depression, including moclobemide, tranylcypromine, phenelzine, pargyline
• sumatriptan, another similar medicine used to treat migraine

Some medicines, herbal products, or dietary supplements may interact with rizatriptan. These include:

• propranolol, a medicine used to treat high blood pressure
• ergotamine, dihydroergotamine, other medicines used to treat migraine
• methysergide, a medicine used to prevent migraine
• St. John's wort (Hypericum perforatum), a herbal product sold as a dietary supplement, or products containing St. John's wort

These medicines, herbal products, or dietary supplements may be affected by rizatriptan, or may affect how well it works. If you are taking any of these you may need a different dose or you may need to take different medicines or you may need to be careful of the timing of some of these medicines.

Ask your doctor for instructions about taking rizatriptan if you are also 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.

Other medicines not listed above may also interact with rizatriptan.

Your doctor has more information on medicines to be careful with or avoid while taking rizatriptan.

How to take this medicine

Follow carefully all directions given to you by your doctor. Their instructions may be different to the information in this leaflet.

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

The usual dose to treat a migraine is one 10 mg.

If the first rizatriptan tablet does help your migraine, but it comes back later, you may take another tablet.

Take the second tablet at least 2 hours after the first. Do not take more than 30 mg (three 10 mg tablets) in a 24 hour period.

If the first rizatriptan tablet does not help your migraine, do not take another tablet for the same attack as it is unlikely to help. It is still likely, however, that you will respond to rizatriptan during your next attack.

You should not take rizatriptan10mg while you are taking propranolol.

If you do not understand the instructions on the box, ask your doctor for help.

Do not stop taking your medicine or change your dosage without first checking with your doctor.

How to take it

With dry hands place the tablet on your tongue.

When to take it

Take this medicine at the same time each day. Taking it at the same time each day will have the best effect and will also help you remember when to take it.

It does not matter if you take it before, with or after food.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If it is almost time to take your next dose, skip the missed dose and take your next dose at the usual time. Otherwise, take it as soon as you remember and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for missed doses.

This may increase the chance of you experiencing side effects.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints to help you remember.

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively, go to the Accident and Emergency department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too many tablets, you may feel sleepy, dizzy, faint or have a slow heartbeat.

While you are taking this medicine

Things you must do

If your headache is more severe than your 'usual' migraine or behaves differently, tell your doctor.

Tell your doctor that you are taking this medicine if:

• you are about to be started on any new medicine
• you are pregnant or are planning to become pregnant
• you are breastfeeding or are planning to breast-feed
• you are about to have any blood tests
• you are going to have surgery or an anaesthetic or are going into hospital.

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

Things you must not do

Do not:

• Give this medicine to anyone else, even if their symptoms seem similar to yours.
• Take your medicine to treat any other condition unless your doctor tells you to.
• Stop taking your medicine, or change the dosage, without first checking with your doctor.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you.

Migraine or treatment with rizatriptan may cause sleepiness or dizziness in some people. Make sure you know how you react to rizatriptan before you drive a car, operate machinery, or do anything else that could be dangerous if you are sleepy or dizzy. If you drink alcohol, sleepiness or dizziness may be worse.

Possible side effects

Tell your doctor as soon as possible if you do not feel well while you are taking rizatriptan or if you have any questions or concerns.

Rizatriptan helps most people with migraine headaches, but they may have unwanted side effects in a few people. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

Tell your doctor if you notice any of the following:

1. difficulty thinking or working because of:

• sleepiness, tiredness
• dizziness
• inability to sleep
• decreased mental sharpness
• nervousness
• agitation
• seeing/ feeling/ hearing things that are not there
• headache not relieved by rizatriptan

2. stomach or bowel problems

• feeling sick (nausea),
• vomiting
• stomach upset or pain
• diarrhoea

3. changes in your sight or taste such as:

• blurred vision
• dry mouth
• thirst
• bad taste
• throat discomfort
• tongue swelling

4. skin problems

• skin rash, itching
• redness or flushing of the face
• hot flushes, sweating

5. changes in the way your body feels, such as:

• feelings of heaviness or tightness on parts of the body
• muscle weakness
• muscle pain
• tingling or numbness of the
• hands or feet
• tremor, unsteadiness when walking
• spinning sensation, also called vertigo
• very high temperature
• unusually increased reflexes or lack of coordination

6. fast, slow or irregular heartbeats, palpitations
7. neck pain or facial pain

Dizziness, sleepiness and tiredness are the most common side effects of rizatriptan. For the most part, these have been mild.

Abnormalities of the electrocardiogram (a test that records the electrical activity of your heart) have also been reported.

If you take rizatriptan too often, you may get chronic headaches. Contact your doctor as you may have to stop taking rizatriptan.

If you experience any of the following, stop taking your medicine and contact your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

These are serious side effects and you may need urgent medical attention or hospitalisation. Serious side effects are rare:

• fainting, coma
• pinkish, itchy swellings on the skin, also called hives or nettlerash
• swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
• shortness of breath, wheezing
• pain or tightness in chest (which may be symptoms of heart attack or angina)
• collapse, numbness or weakness of the arms or legs, headache, dizziness and confusion, visual Other side effects not listed above may occur in some patients. disturbance, difficulty swallowing, slurred speech and loss of speech (which may be symptoms of stroke)
• severe skin reaction which starts with painful red areas, then large blisters and ends with peeling of layers of skin. This is accompanied by fever and chills, aching muscles and generally feeling unwell.
• seizures, fits or convulsions
• persistent purple discolouration, and/or pain in the fingers, toes, ears, nose or jaw
• pain or spasms in the lower stomach, bloody diarrhoea and fever

As with other medicines in the same class as rizatriptan, heart attack, angina and stroke have been reported very rarely, and generally occurred people with risk factors for heart or blood vessel disease (including high blood pressure, diabetes, smoking, family history of heart or blood vessel disease e.g. stroke).

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice any other effects.

Allergic reactions

If you think you are having an allergic reaction to rizatriptan, do not take any more of this medicine and tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

Symptoms of an allergic reaction may include some or all of the following:

• cough, shortness of breath, wheezing or difficulty breathing
• swelling of the face, lips, tongue, throat or other parts of the body
• rash, itching or hives on the skin
• fainting
• hay fever-like symptoms.

Storage and disposal

Storage

Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 30°C.

Do not store your medicine, or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or it has passed its expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What APO-Rizatriptan orally disintegrating tablets looks like

Rizatriptan orally disintegrating tablets are available in two strengths:

5mg: White to off-white coloured, round-shaped tablets with "APO" engraved on one side and "RZ" over "5" on the other side.

Blister Pack of 2 tablets.

10mg: White to off-white coloured, round-shaped tablets with "APO" engraved on one side and "RZ" over "10" on the other side.

Blister Pack of 2 tablets.

* Not all strengths, pack types and/or pack sizes may be available.

Ingredients

Each tablet contains rizatriptan benzoate (equivalent to 5 mg or 10 mg of rizatriptan, respectively).

It also contains the following inactive ingredients:

• Cellulose-microcrystalline
• Mannitol
• Crospovidone
• Sucralose
• Magnesium stearate
• Peppermint flavour.

This medicine is gluten-free, lactose-free, sucrose-free, tartrazine-free and free of other azo dyes.

Australian Registration Numbers

APO-Rizatriptan 5mg orally disintegrating tablets (blister pack): AUST R 222327

APO-Rizatriptan 10mg orally disintegrating tablets (blister pack): AUST R 222334

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113

APO and APOTEX are registered trade marks of Apotex Inc.

This leaflet was last updated in:
March 2016

1 Name of Medicine

Rizatriptan benzoate.

6.7 Physicochemical Properties

Chemical name: N,N-dimethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indole-3-ethanamine monobenzoate.
Molecular formula: C₁₅H₁₉N₅.C₇H₆O₂.
Molecular weight: 391.47 (free base: 269.4).
Rizatriptan benzoate is a white to off-white, crystalline solid; it is soluble in water at about 42 mg/mL (expressed as free base) at 25°C.

Chemical structure.

CAS number.

2 Qualitative and Quantitative Composition

Each orally disintegrating tablet contains either 5 mg or 10 mg rizatriptan (corresponding to 7.265 mg or 14.53 mg rizatriptan benzoate, respectively) as the active ingredient.

Excipients with known effect.

3 Pharmaceutical Form

5 mg orally disintegrating tablet.

10 mg orally disintegrating tablet.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

Rizatriptan wafers.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

Characteristics in patients.

Gender.

Elderly.

Hepatic impairment.

Renal impairment.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

4 Clinical Particulars

4.1 Therapeutic Indications

Rizatriptan is indicated for the acute treatment of migraine attacks with or without aura.

4.3 Contraindications

This medicine is contraindicated in patients with:
hypersensitivity to rizatriptan or any of the ingredients in the tablet;
concurrent administration of monoamine oxidase (MAO) inhibitors, or use within 2 weeks of discontinuation of MAO inhibitor therapy (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Based on the mechanism of action of this class of compounds, rizatriptan is also contraindicated in patients with:
uncontrolled hypertension;
established coronary artery disease, including ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), signs and symptoms of ischemic heart disease, or Prinzmetal's angina;
history of stroke or transient ischemic attack (TIA);
peripheral vascular disease, including (but not limited to) ischemic bowel disease.

4.4 Special Warnings and Precautions for Use

Rizatriptan should only be administered to patients in whom a clear diagnosis of migraine has been established. Rizatriptan should not be administered to patients with basilar or hemiplegic migraine.
Rizatriptan should not be used to treat "atypical" headaches, i.e. those that might be associated with potentially serious medical conditions (e.g. stroke, ruptured aneurysm) in which cerebrovascular vasoconstriction could be harmful.
There have been rare reports of serious coronary events with this class of drugs including rizatriptan (see Section 4.8 Adverse Effects (Undesirable Effects)). Prior to prescribing this drug, cardiovascular assessment should be considered in patients at risk for coronary artery disease (CAD) [e.g. patients with hypertension, diabetics, smokers, and those with strong family history for CAD]. Those in whom CAD is established should not be given rizatriptan (see Section 4.3 Contraindications).
Other 5-HT_1B/1D agonists (e.g. sumatriptan) should not be used concomitantly with rizatriptan.
Administration of ergotamine type medications (e.g. ergotamine, dihydro-ergotamine or methysergide) and rizatriptan within 6 hours of each other is not recommended. 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.
Cases of life threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake inhibitors (SSRIs)/ serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans. If concomitant treatment with rizatriptan and an SSRI (e.g. sertraline, escitalopram oxalate, and fluoxetine) or SNRI (e.g. venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Overuse of acute migraine drugs may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

Use by gender or in individuals of various ethnic origins.

Use in the elderly.

Paediatric use.

Children (under 12 years of age).

Adolescents (12-17 years of age).

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacokinetic interactions.

Cytochrome P450 isoforms.

Monoamine oxidase inhibitors.

Beta-blockers.

Selective serotonin reuptake inhibitors/ serotonin norepinephrine reuptake inhibitors and serotonin syndrome.

Paroxetine.

Oral contraceptives.

Experience in migraine patients.

St. John's wort (Hypericum perforatum).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.8 Adverse Effects (Undesirable Effects)

Adverse experiences were assessed in controlled clinical trials in which over 3,600 patients received single or multiple doses of rizatriptan. More than 1,500 patients were treated in long-term extension studies for up to one year.
In clinical trials, rizatriptan was generally well tolerated. Adverse experiences were typically mild in intensity and transient. The most common drug related adverse experiences were dizziness, somnolence, and asthenia/ fatigue. Table 1 lists drug related adverse experiences in acute phase III trials in outpatients with migraine.
Additional drug related adverse experiences in patients taking 1 or more doses of rizatriptan 5 mg or 10 mg during acute (incidence ≥ 1% and greater than placebo) or long-term (incidence ≥ 1%) clinical trials were, by body system, as follows.

Body as a whole.

Cardiovascular.

Digestive.

Musculoskeletal.

Nervous system.

Respiratory.

Skin.

Special senses.

Urogenital.

Postmarketing experience.

Hypersensitivity.

Musculoskeletal.

Special senses.

Nervous system.

Vascular disorders.

Cardiac disorders.

Gastrointestinal disorders.

Investigations.

Reporting suspected adverse effects.

4.2 Dose and Method of Administration

APO-Rizatriptan orally disintegrating tablets are intended for oral administration.
Administration with liquid is not necessary.
Patients should be instructed not to remove the tablet from the blister until just prior to dosing. The tablet should be removed with dry hands and the tablet placed on the tongue, where it will dissolve and be swallowed with the saliva.

Dosage.

Redosing.

For headache recurrence within 24 hours.

After nonresponse.

Patients receiving propranolol.

4.7 Effects on Ability to Drive and Use Machines

Migraine or treatment with rizatriptan may cause somnolence in some patients. Dizziness has also been reported in some patients receiving rizatriptan. Patients should, therefore, evaluate their ability to perform complex tasks during migraine attacks and after administration of rizatriptan.

4.9 Overdose

No overdoses of rizatriptan were reported during clinical trials.
Rizatriptan 40 mg (administered as either a single dose or as two doses with a 2 hour interdose interval) was generally well tolerated in over 300 patients; dizziness and somnolence were the most common drug related adverse effects.
In a clinical pharmacology study in which 12 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, and a 5 second systolic pause (on ECG monitor) immediately after a 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. Gastrointestinal decontamination (e.g. gastric lavage followed by activated charcoal) should be considered in patients suspected of an overdose with rizatriptan. Clinical and electrocardiographic monitoring should be continued for at least 12 hours, even if clinical symptoms are not observed.
The effects of haemodialysis or peritoneal dialysis on serum concentrations of rizatriptan are unknown.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, mannitol, crospovidone, sucralose, magnesium stearate and peppermint flavour (PI No. 109068).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

5 mg orally disintegrating tablet.

10 mg orally disintegrating tablet.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes