Consumer medicine information

Clustran

Sumatriptan

BRAND INFORMATION

Brand name

Clustran

Active ingredient

Sumatriptan

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Clustran.

SUMMARY CMI

Clustran

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Clustran?

Clustran contains the active ingredient sumatriptan succinate. Clustran is used to relieve a migraine attack or cluster headache with or without what is known as ‘aura’. For more information, see Section 1. Why am I using Clustran? in the full CMI.

2. What should I know before I use Clustran?

Do not use if you have ever had an allergic reaction to sumatriptan succinate or any of the ingredients listed at the end of the CMI, or latex (the syringe needle shield may contain latex).

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Clustran? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Clustran and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Clustran?

The first time you ever have Clustran it must be under the supervision of a doctor. The recommended dose for adults aged 18 to 65 years is one injection pen of 6 mg, just under the skin, on the outside of the thigh. If the first Clustran helps your migraine or cluster headache, but the headache/migraine comes back later, you may use another Clustran. You must wait at least one hour between using the first and second Clustran. Do not use more than 2 pre-filled pens (2 x 6 mg) in any twenty-four hours.

More instructions can be found in Section 4. How do I use Clustran? in the full CMI.

5. What should I know while using Clustran?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Clustran.
  • Tell your doctor if, for any reason you have not taken your medicine exactly as directed.
  • Tell your doctor if you become pregnant or are trying to become pregnant.
Things you should not do
  • Do not give this medication to anyone else, even if their symptoms seem similar to yours.
Driving or using machines
  • Be careful driving or operating machinery until you know how Clustran affects you. Clustran may cause drowsiness in some people.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep this medicine where children cannot reach it, such as in a locked cupboard.
  • Keep Clustran in a cool, dry place where it stays below 25°C and protect from light.
  • Keep Clustran in its pack until time to use.

For more information, see Section 5. What should I know while using Clustran? in the full CMI.

6. Are there any side effects?

Common side effects include pain, tingling, heat or flushing in any part of the body, feeling of sleepiness, dizziness or tiredness, nausea or vomiting, a change in blood pressure, feelings of faintness, problem with your eyesight, pain in the lower tummy and bloody diarrhea, shaking or tremors, uncontrolled movements, shortness of breath. Some serious side effects include irregular heartbeats, fits or convulsion, wheezing or swelling of the lips/mouth, difficulty in breathing, hay fever, lumpy rash (“hives”), fainting, feelings of heaviness, pressure or tightness in any part of the body including the chest or throat, or have persistent purple discoloration and/or pain in the fingers, toes, ears, nose or jaw in response to cold.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Clustran

Active ingredient: Sumatriptan succinate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Clustran. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Clustran.

Where to find information in this leaflet:

1. Why am I using Clustran?
2. What should I know before I use Clustran?
3. What if I am taking other medicines?
4. How do I use Clustran?
5. What should I know while using Clustran?
6. Are there any side effects?
7. Product details

1. Why am I using Clustran?

Clustran contains the active ingredient sumatriptan succinate. This medicine belongs to a group of drugs called serotonin agonists.

Clustran is used to relieve a migraine attack or cluster headache. It should not be used to prevent migraine attacks or cluster headaches from occurring. Clustran may be used for migraine headaches with or without what is known as 'aura'.

It is thought that migraine headaches and cluster headaches are due to widening of certain blood vessels in the head. Clustran works by making those vessels normal again and eases the symptoms of migraine and cluster headaches.

Clustran does not work in other types of headache which are not a migraine or a cluster headache.

Clustran should not be administered to patients with hemiplegic, basilar or ophthalmoplegic migraine.

Clustran is not addictive.

2. What should I know before I use Clustran?

Warnings

Do not use Clustran if:

  • you are allergic to sumatriptan succinate, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
  • you are allergic to latex (the syringe needle shield may contain latex).
  • you have or have had heart disease or heart attack.
  • you have or have had shortness of breath, pain or tightness in chest, jaw or upper arm.
  • you have or have had peripheral vascular disease (pain in the back of the legs) or are prone to cold, tingling or numb hands and feet.
  • you have or have had Prinzmental's angina (an uncommon form of angina where pain is experienced at rest rather than during activity).
  • you have or have had angina and/or severe chest pain or tightness.
  • you have or have had high blood pressure.
  • you have or have had severe liver disease.
  • you have or have had stroke or mini stroke (TIAs)
  • you have taken any of the following medication in the last 24 hours:
    - ergotamine (e.g. Cafergot)
    - dihydroergotamine (e.g. Dihydergot)
    - methsergide (e.g. Deseril)
    - naratriptan (e.g. Naramig)
    - zolmitriptan (e.g. Zomig).
  • you have taken any of the following medicines in the last two weeks:
    - Monoamine oxidase inhibitors (MAOIs), a type of medication used for depression.
    - SSRIs (Selective Serotonin Reuptake Inhibitors) or SNRIs (Serotonin-noradrenaline Reuptake Inhibitors) used to treat depression.
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn or shows signs of tampering.

Tell your doctor if you:

  • are allergic to foods, dyes, preservatives, or any other medicines, including any that contain sulfur (e.g. sulfonamide antibiotics).
  • you are taking or have taken medicines in the last two weeks, including medicines you buy without a prescription, particularly herbal preparations containing St John's Wort and medicines prescribed for depression.
  • you have or have had medical conditions like:
    - liver or kidney problems.
    - heart problems. Risk factors including high blood pressure even if it is under control, a family history of heart problems.
    - high blood cholesterol levels, obesity, diabetes, you are a male and over 40 years of age, you are female and have undergone menopause or you smoke.
    - epilepsy, seizures, or fits or been told that you are prone to this problem.
    - stroke.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Clustran and affect how it works.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Clustrn.

4. How do I use Clustran?

How much to use

For adults aged 18 to 65, the dose is one injection pen of 6 mg.

If the first Clustran helps your migraine or cluster headache, but the headache/migraine comes back later, you may use another Clustran. You must wait at least one hour between using the first and second Clustran.

Do not use more than 2 pre-filled pens (2 x 6 mg) in any twenty-four hours.

Do not use a second pre-filled pen, if the first has not provided any relief from your symptoms. You may take your usual headache relief medication provided it does not contain ergotamine or methysergide. If you are not sure what to do, ask your doctor or pharmacist.

If your migraine or cluster headache is not relieved by Clustran, you may use Clustran on another occasion to treat another attack. Provided there are no side effects, you can use Clustran to treat at least three separate migraine or cluster headache attacks before you and your doctor decide this medicine is ineffective for you.

When to use Clustran

  • when the migraine headache or cluster headache begins; or
  • when other symptoms of the migraine begin, such as nausea (feeling sick), vomiting or your eyes becoming sensitive to light.

If you use Clustran later during the attack it will still work for you. Do not use your Clustran before the above symptoms occur.

How to use Clustran

The first time you ever have Clustran it must be under the supervision of a doctor. After this you must use the injection as your doctor has instructed.

See the Patient Instructions For Use below or overleaf for information on how to use the pre-filled pen and how to discard it. If there is something you do not understand, ask your doctor or pharmacist.

Clustran should be injected just under the skin on the outside of the thigh using the pre-filled pen.

If you use too much Clustran

If you think that you have used too much Clustran, you may need urgent medical attention.

You should immediately:

  • In Australia: phone the Poisons Information Centre
    (by calling 13 11 26), or
    In New Zealand: phone the National Poisons Centre on 0800 POISON (0800 764 766), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Clustran?

Things you should do

Tell your doctor or pharmacist if, for any reason, you have not taken your medicine exactly as directed.

Otherwise, your doctor or pharmacist may think that is not working and change your treatment unnecessarily.

Remind any doctor, dentist or pharmacist you visit that you are using Clustran.

Things you should not do

Do not give his medicine to anyone else, even if their symptoms seem similar to yours.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Clustran affects you.

As with many other medicines, Clustran may cause drowsiness in some people.

If you use Clustran too often, it may make your headache worse. If this happens, your doctor may tell you to stop using Clustran.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep your pre-filled pen where children cannot reach them, such as in a locked cupboard.
  • Keep Clustran in a cool, dry place where it stays below 25°C and protect from light. Brief temperature excursions below and above 25°C permitted.
  • Do not leave in a car, on a window sill or in a bathroom.
  • Keep Clustran in its pack until time to use.

Product is for single use in one patient only. Discard any residue.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • temporary pain at the site of injection.
  • pain, tingling, heat or flushing in any part of the body.
  • feelings of sleepiness, dizziness or tiredness.
  • nausea (feeling sick) or vomiting.
  • a change in blood pressure.
  • feelings of faintness.
  • problem with your eyesight.
  • pain in the lower tummy and bloody diarrhoea (ischaemic colitis).
  • shaking or tremors.
  • uncontrolled movements.
  • shortness of breath.
  • if you had a recent injury or inflammation (like rheumatism or inflammation of the colon) you may experience pain or pain worsening or inflammation.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

serious side effectsWhat to do
  • feel heaviness, pressure or tightness in any part of the body including the chest or throat.
  • feel irregular heartbeats.
  • have a fit or convulsion.
  • wheezing, swelling of the lips/mouth, difficulty in breathing, hay fever, lumpy rash ("hives") or fainting. These could be a symptom of an allergic reaction.
  • have persistent purple discolouration and/or pain in the fingers, toes, ears, nose or jaw in response to cold.
Call your doctor straight away, or; go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to:
In Australia: The Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems, or
In New Zealand: The Centre for Adverse Reactions Monitoring (CARM) via pophealth.my.site.com/carmreportnz/s/

By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Clustran contains

Active ingredient
(main ingredient)		Sumatriptan succinate
Other ingredients
(inactive ingredients)		sodium chloride
water for injection
Potential allergenslatex (the syringe needle shield may contain latex)

Do not take this medicine if you are allergic to any of these ingredients.

What Clustran looks like

Clustran is packed in a box containing either one or two pre-filled pens. Each Clustran pre-filled pen contains one dose of 6 mg sumatriptan (as succinate) in 0.5 mL of solution.

Not all pack sizes may be marketed in Australia or New Zealand.

Australia Registration Number AUST R 209316

Who distributes Clustran

Australia

Sun Pharma ANZ Pty Ltd
12 Waterloo Road
Macquarie Park
Sydney NSW 2113
Australia
[email protected]
Tel: 1800 726 229

New Zealand

Douglas Pharmaceuticals Ltd
P O Box 45 027
Auckland 0651
New Zealand
Phone: (09) 835 0660

This leaflet was prepared in June 2024

INSTRUCTIONS ON HOW TO USE CLUSTRAN

This leaflet explains how to give a dose of Clustran.

Read these instructions TWICE before you begin the first step. If you have any questions, ask your doctor or pharmacist.

PRECAUTIONS:

  • Check the appearance of the medicine, through the inspection window (figure 1). It must be a clear, colourless to pale yellow solution. Do not inject the solution if it looks discoloured or cloudy or contains lumps, flakes, or particles.
  • Do not remove the white needle shield from the pre-filled pen until you are ready to inject.
  • NEVER put the white needle shield back into the pre-filled pen.
  • When the white needle shield is removed NEVER put or press, thumb, fingers, or hand over the exposed grey tip.

PREPARING TO ADMINISTER CLUSTRAN

  1. Wash your hands thoroughly.
  2. Check the appearance of the medicine, through the inspection window (figure 1). It must be a clear, colourless to pale yellow solution. Do not inject the solution if it looks discoloured or cloudy or contains lumps, flakes, or particles.
  3. Gather all the equipment you will need (Clustran and alcohol or sterile swabs)
  4. Identify the application area (figure 2).
  • Usually the outer thigh or somewhere with an adequate fatty tissue layer.
  • Do not inject into areas where the skin is tender, bruised, red, or hard.
  1. Wipe the injection site with alcohol or a sterile swab.
  • Allow your skin to dry.
  • Do not touch this area again before giving the injection.

HOW TO INJECT CLUSTRAN

PULLRemove the white needle shield by pulling it straight off (Figure 3).
  • Do not bend or twist-off the white needle shield.
  • Do not put the white needle shield back on as this may damage the needle inside.

PLACEWithout pushing the blue activation button, place Clustran on the injection site, completely depressing grey tip (Figure 4).
  • Place the open end on the site at a 90°angle (Figure 4a).
  • Push the grey tip firmly against the skin to unlock (Figure 4a and 4b).
  • The grey tip must be completely depressed to inject the medication (Figure 4b).

PRESSPress the blue activation button, hear the click and release your thumb (Figure 5a)
  • The first click will sound. Immediately release your thumb (Figure 5a).
    (The blue activation button will not work if the safety needle cover is not completely depressed.)

HOLDHold Clustran in place until you hear the second 'click' (Figure 5b).
  • If you did not remove your thumb from the blue button, the second 'click' cannot be heard. If this happens, slowly count to 15 to ensure the full dose is delivered.
  • The inspection window will turn blue, confirming the injection is complete. If the inspection window is not blue, do not try to use the pre-filled pen again.

REMOVERemove Clustran by lifting it straight up from the injection site (Figure 5b).
  • The needle safety cover will automatically extend and lock into place to conceal the needle (Figure 5b and 6).
  • There is no need to replace the white needle shield.
  • Do not rub the injection site. If you notice a spot of blood at the injection site, dab away with a cotton ball or tissues. If needed, you may cover the injection site with a bandage.

NEVER ATTEMPT TO REUSE A Clustran pen.

If you suspect you have not received the full dose, DO NOT repeat the injection using a new Clustran pen for at least 1 hour. Do not use more than two Clustran pens in any 24 hour period

STORAGE:

Store below 25°C. Protect from light. Brief temperature excursions below and above 25°C permitted.

Published by MIMS October 2024

BRAND INFORMATION

Brand name

Clustran

Active ingredient

Sumatriptan

Schedule

S4

 

1 Name of Medicine

Sumatriptan (as succinate).

2 Qualitative and Quantitative Composition

Sumatriptan succinate is the therapeutically active ingredient in Clustran.

Clustran 6 mg/0.5 mL injection syringe with autoinjector.

Each pre-filled pen contains sumatriptan (as succinate) 6 mg in 0.5 mL solution.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clustran sumatriptan (as succinate) 6 mg/0.5 mL is a clear colorless to pale yellow solution in prefilled syringe, in an autoinjector drug delivery device.

4 Clinical Particulars

4.1 Therapeutic Indications

Clustran is indicated for the acute relief of migraine attacks with or without aura.
Clustran is also indicated for the acute treatment of cluster headaches.
There is no information available on the use of sumatriptan in the treatment of basilar or hemiplegic migraine.

4.2 Dose and Method of Administration

Product is for single use in one patient only. Discard any residue.
Clustran is indicated for the acute intermittent relief of both migraine and cluster headache. It should not be used prophylactically.
Ergotamine or ergotamine derivatives and Clustran should not be administered concurrently (see Section 4.3 Contraindications).
Clustran should be injected subcutaneously. Patients should be advised to observe strictly the instruction leaflet for the Clustran, especially regarding the safe disposal of the pen device (autoinjector).
The first dose of Clustran should be given by, or under the direct supervision of, a physician. As with the administration of the first dose of any injectable therapeutic product, appropriate resuscitative equipment should be available. Appropriate advice on the future use of Clustran by the patient should also be given at this time. The physician should ensure that the patient is familiar with and understands the Consumer Medicine Information.

Migraine.

It is recommended to start the treatment at the first sign of a migraine headache or associated symptoms such as nausea, vomiting or photophobia. The efficacy of sumatriptan is independent of the duration of the attack when starting treatment. Administration during a migraine aura prior to other symptoms occurring may not prevent the development of a headache.
If a patient does not respond to the first dose of Clustran, a second dose should not be taken for the same attack. Clustran may be used for subsequent attacks.
The recommended adult dose of Clustran is a single 6 mg, subcutaneous injection. If symptoms recur a further subcutaneous dose of 6 mg may be given at any time in the next 24 hours provided that one hour has elapsed since the first dose. The maximum dose in 24 hours is 2 x 6 mg injections (12 mg).

Cluster headache.

The recommended adult dose is a single 6 mg subcutaneous injection for each cluster attack. The maximum dose in 24 hours is two 6 mg injections (12 mg) providing at least one hour has elapsed between injections.
For information on use in children, adolescents and elderly, see Section 4.4 Special Warnings and Precautions for Use.

4.3 Contraindications

Sumatriptan should not be used in patients who have:
hypersensitivity to any component of the preparation (see Section 6.1 List of Excipients);
a history of myocardial infarction;
peripheral vascular disease or symptoms or signs consistent with ischaemic heart disease;
Prinzmetal's angina/coronary vasospasm;
uncontrolled hypertension;
cerebrovascular accident (CVA) or transient ischaemic attack (TIA);
severe hepatic impairment.
Sumatriptan should not be used within 24 hours of treatment with an ergotamine-containing or ergot-type medication such as dihydroergotamine or methysergide.
Sumatriptan should not be administered to patients with severe hepatic impairment.
Sumatriptan should not be given to patients receiving monoamine oxidase inhibitors (MAOIs) or within two weeks of discontinuation of MAOI therapy (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Sumatriptan should not be administered to patients with hemiplegic, basilar or ophthalmoplegic migraine.

4.4 Special Warnings and Precautions for Use

General.

Sumatriptan should only be used where there is a clear diagnosis of migraine. However, if a patient does not respond to the first dose, the opportunity should be taken to review the diagnosis before a second dose is given. The recommended doses of sumatriptan should not be exceeded.
Drowsiness may occur as a result of migraine or its treatment with sumatriptan. Caution is recommended in patients performing skilled tasks, e.g. driving or operating machinery.
Sumatriptan should also be administered with caution to patients with diseases which may affect significantly the metabolism, absorption and excretion of the drug, such as impaired hepatic or renal function. Studies have shown reduced sumatriptan clearance in patients with hepatic impairment. Lower doses should be considered in these patients. If appropriate, the first dose should be given under supervision to these patients.
Patients with known hypersensitivity to sulphonamides may exhibit an allergic reaction following administration of sumatriptan. Reactions may range from cutaneous hypersensitivity to anaphylaxis. Evidence of cross sensitivity is limited, however, caution should be exercised before using sumatriptan in these patients.

Latex or rubber allergy.

The needle shield of the pre-filled syringe may contain dry natural latex rubber that has the potential to cause allergic reactions in latex sensitive individuals.
Patients should be advised to pay strict attention to the instruction leaflet for sumatriptan injection, especially regarding the safe disposal of the pen device (autoinjector).
Overuse of acute migraine treatments has been associated with the exacerbation of headache (medication overuse headache, MOH) in susceptible patients. Withdrawal of the treatment may be necessary.
Reversible cerebral vasoconstriction syndrome (thunderclap headache) has been reported with use of serotonergic agents such as SSRIs or triptans (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Co-administration of sumatriptan within 24 hours of other 5-HT1 agonists is not recommended due to the potential for vasoconstrictive effects.

Cardiovascular.

It is strongly recommended that sumatriptan not be given to patients in whom risk factors indicate a possibility of unrecognised coronary artery disease (CAD) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischaemic myocardial disease or other significant underlying cardiovascular disease. The risk factors include hypertension, hypercholesterolaemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best and, in extremely rare cases (less than 1 in 10,000), serious cardiac events have occurred in patients without underlying cardiovascular disease. If during the cardiovascular evaluation, the patient's medical history of electrocardiographic investigations reveal findings indicative of, or consistent with coronary artery vasospasm or myocardial ischaemia, sumatriptan should not be administered (see Section 4.3 Contraindications).
Sumatriptan may cause short lived elevation of blood pressure and peripheral vascular resistance. Sumatriptan should therefore be administered with caution to patients with controlled hypertension. Transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients.
Serious cardiac events, including some that have been fatal, have occurred within a few hours following the use of sumatriptan Injection. These events are extremely rare (less than 1 in 10,000) and the majority of these case reports were confounded by patients having pre-existing heart disease or risk factors for ischaemic heart disease and may reflect underlying disease and spontaneous events. Under these circumstances the specific contribution of sumatriptan cannot be determined. Events reported have included coronary artery vasospasm, transient myocardial ischaemia, myocardial infarction, and cardiac arrhythmias including ventricular tachycardia and ventricular fibrillation. Therefore sumatriptan should not be given to patients in whom unrecognised cardiac disease is likely without a prior evaluation for underlying cardiovascular disease. Such patients include postmenopausal women, males over 40 and patients with risk factors for coronary artery disease. Significant cardiovascular sequelae have been reported in patients in whom risk factors were not readily identifiable. There is no experience in patients with recent cardiac arrhythmias (especially tachycardias). Until further information is available, the use of sumatriptan is not recommended in these patients.
A myocardial infarct has been reported in a 14 year old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration.
When given intravenously sumatriptan can cause angina in susceptible patients. Sumatriptan injection should therefore not be given intravenously.
Following administration, sumatriptan can be associated with transient symptoms, including chest pain and tightness, which may be intense and involve the throat. If symptoms consistent with ischaemic heart disease occur, appropriate investigations should be carried out and further doses should not be given until the results of these investigations are known. Patients should be advised to contact their doctor immediately if they experience symptoms consistent with ischaemic heart disease (see Section 4.3 Contraindications).

Cerebrovascular.

Cerebral haemorrhage, subarachnoid haemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with oral or subcutaneous sumatriptan, and some have resulted in fatalities. The relationship of sumatriptan to these events is uncertain. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Sumatriptan should not be administered if the headache being experienced is atypical of the patient. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g. cerebrovascular accident, transient ischaemia attack).
Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions.
Sumatriptan should be used with caution in patients with a history of seizures or other risk factors which lower the seizure threshold.
There is no experience in patients with recent cerebrovascular accidents. Until further information is available, the use of sumatriptan is not recommended in these patients (see Section 4.3 Contraindications).
There is no information available on the use of sumatriptan in the treatment of ophthalmoplegic migraine.

Other vasospastic events.

Sumatriptan may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischaemia and colonic ischaemia with abdominal pain and bloody diarrhoea have been reported.

Ophthalmic.

Intermittent transient changes on the surface of the cornea have been observed in toxicology studies in dogs. No causative mechanism has been established for these changes but there is no evidence to suggest that this is relevant to clinical exposure.

Use in the elderly.

Patients over 65 years.

Experience of the use of sumatriptan in patients aged over 65 is limited. However the pharmacokinetics do not differ significantly from a younger population. Until further clinical data are available, the use of sumatriptan in patients aged over 65 is not recommended.

Paediatric use.

Adolescents (12-17 years) and children (under 12 years).

The efficacy of oral sumatriptan has not been established in placebo-controlled trials carried out in 794 adolescent migraineurs. High placebo responses were found in these studies and there was a lack of statistically significant difference between placebo and oral doses ranging from 25 to 100 mg. The safety profile of oral and intranasal sumatriptan is similar to that of adults. The safety and effectiveness of sumatriptan in children under the age of 12 years has not been established.

Effects on laboratory.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacodynamic.

Prolonged vasospastic reactions have been reported with ergotamine. As these effects may be additive, concomitant use of ergotamine or ergotamine derivatives and sumatriptan should be avoided. Twenty-four hours should elapse before sumatriptan is taken following any ergotamine containing preparation. Conversely, ergotamine containing preparations should not be taken until 6 hours have elapsed following sumatriptan administration (see Section 4.3 Contraindications).

Pharmacokinetic.

An interaction may occur between sumatriptan and MAOIs and concomitant administration is contraindicated (see Section 4.3 Contraindications). Rarely an interaction may occur between sumatriptan and selective serotonin reuptake inhibitors. There have been rare post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability, neuromuscular abnormalities, weakness, hyper-reflexia and incoordination) following the use of a SSRI. Serotonin syndrome has been reported following concomitant treatment with triptans and serotonin noradrenaline reuptake inhibitors (SNRIs).
If concomitant treatment with sumatriptan and a SSRI/SNRI is clinically warranted, appropriate observation of the patient is advised.
The concomitant administration of any triptan/5-HT1 agonist with sumatriptan is not recommended.
There is no evidence of interactions with propranolol, flunarizine, pizotifen or alcohol.
Although there is no clear evidence, it is possible that an interaction may occur between serotonin 5-HT1 agonists and the herbal remedy St John's wort (Hypericum perforatum), which may result in an increase in side effects.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
No obvious teratogenic effects have been seen in rats given oral doses of 500 mg/kg and intravenous doses up to 12.5 mg/kg or in rabbits given oral doses up to 100 mg/kg and intravenous doses up to 8 mg/kg during organogenesis (although it is noted that the number of pregnant rabbits investigated was limited).
Reproduction studies in rats have not revealed any clear evidence of impaired fertility (oral doses up to 500 mg/kg, subcutaneous doses up to 60 mg/kg, given before and during mating) or of impaired post-natal pup development (oral doses up to 1000 mg/kg, subcutaneous doses up to 81 mg/kg, given during the peri and post-natal period).
In the rabbit embryotoxicity cannot be ruled out. After oral administration, at doses of 5, 25 and 100 mg/kg on days 8-20 of gestation (severe maternal toxicity at 100 mg/kg) there was evidence of a small, increasing dose-related trend in post-implantation intrauterine death with a similar, and significant trend being recorded after intravenous treatment (0.5 to 8 mg/kg, days 8-20 of gestation).
When administered to pregnant rabbits throughout the period of organogenesis sumatriptan has occasionally caused embryolethality at doses which were sufficiently high to produce maternal toxicity.
Term foetuses from Dutch Stride rabbits treated during the period of organogenesis with oral sumatriptan exhibited an increased incidence of cervicothoracic vascular defects and skeletal abnormalities.
Administration of this drug should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
 Sumatriptan is excreted in breast milk in animals. In rats given oral sumatriptan at 1000 mg/kg during the lactation period, 3 dams out of 20 showed total litter loss whilst in another litter, only 9/15 survived to the end of nursing. It has been demonstrated that following subcutaneous administration sumatriptan is excreted into breast milk. Infant exposure can be minimised by avoiding breastfeeding for 24 hours after treatment. Caution should be exercised when considering the administration of sumatriptan to a breast feeding woman.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. Drowsiness may occur as a result of migraine or treatment with sumatriptan. This may influence the ability to drive and to operate machinery.

4.8 Adverse Effects (Undesirable Effects)

The most common side effect associated with treatment with sumatriptan administered subcutaneously is:
transient pain at the site of injection;
stinging/burning, swelling, erythema, bruising and bleeding at the injection site have also been reported.
The most common side effects associated with treatment with sumatriptan are:
Pain, sensations of tingling, heat or cold, heaviness, pressure or tightness. These are usually transient and may be intense and can affect any part of the body including the chest and throat.
Flushing, dizziness and feelings of weakness. These are mostly mild to moderate in intensity and transient.
Fatigue, drowsiness, sensory disturbance including paraesthesia and hypoaesthesia have been reported.
Nausea and vomiting occurred in some patients but the relationship to sumatriptan is not clear.
Transient increases in blood pressure arising soon after treatment have been recorded.
Dyspnoea.
Although direct comparisons are not available, nausea, vomiting and fatigue appear to be less frequent with subcutaneous administration of sumatriptan, than with tablets. Conversely, flushing, paraesthesia and sensations of tingling, heat or cold, pressure and heaviness may be more common after the injection.
Serious coronary events have been reported (see Section 4.4 Special Warnings and Precautions for Use).
Other cardiovascular adverse reactions include hypotension, bradycardia, tachycardia and palpitations. Very rarely (less than 1 in 10,000) Raynaud's phenomenon, angina and ischaemic colitis have been reported.
There have been rare (less than 1 in 1,000) reports of seizures following migraine attacks treated with sumatriptan. Although some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures, there are also reports in patients where no such predisposing factors are apparent.
Patients treated with sumatriptan very rarely (less than 1 in 10,000) exhibit visual disorders like flickering and diplopia. Additionally cases of nystagmus, scotoma and reduced vision have been observed. Very rarely loss of vision has occurred, which is usually transient. However, visual disorders may also occur during a migraine attack itself.
Hypersensitivity reactions ranging from cutaneous hypersensitivity (e.g. rash, urticaria, pruritus or erythema) to, in rare (less than 1 in 10,000) cases, anaphylaxis have been recorded (see Section 4.4 Special Warnings and Precautions for Use).
Minor disturbances of liver function tests have occasionally been observed. There is no evidence that clinically significant abnormalities occurred more frequently than with placebo.
In the clinical trial programme, decreased lymphocyte count post treatment was observed in a number of patients receiving either oral or subcutaneous sumatriptan. This effect was not dose-related and was also observed in patients receiving placebo. The significance of these findings is uncertain.

Post-marketing data.

In addition to the drug-related adverse reactions reported from clinical trials, the following serious spontaneous events, reported to be possibly, probably or almost certainly caused following use of either subcutaneous, oral or intranasal sumatriptan in patients less than 18 years of age have been identified.

Cardiovascular.

Myocardial infarction.

Cerebrovascular.

Cerebellar infarction.

Neurology.

Seizures, tremor and dystonia.

Non-site specific.

Anaphylaxis.

Skin.

Urticaria, rash.

General disorders.

"Pain trauma activated" and "pain inflammation activated" - frequency not known.
Additional adverse effects not observed in the subcutaneous injection dosage form, which were observed in other dosage forms at an incidence presented in Table 1 that of placebo are listed below:
Tablets and nasal spray: palpitations, disturbance of taste, nausea/vomiting;
Nasal spray: throat and tonsil signs and symptoms, burning/stinging sensation;
Tablets: dysphagia, syncope, hypotension, pallor, pulsating sensation, dyspnoea.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals in Australia are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There have been some reports of overdosage with sumatriptan injection. Patients have received single injections of up to 12 mg subcutaneously without significant adverse effects. Single doses of up to 40 mg intranasally, up to 16 mg subcutaneously, and up to 400 mg with sumatriptan tablets orally, were not associated with side effects other than those mentioned. There is no experience of doses greater than these.
If overdosage with Clustran occurs, the patient should be monitored for at least ten hours and standard supportive treatment applied as required.
It is unknown what effect haemodialysis or peritoneal dialysis has on the plasma concentrations of sumatriptan.
For information on the management of overdose contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Sumatriptan has been demonstrated to be a specific vascular 5-hydroxytryptamine-1 (5HT1) receptor agonist with no effect at other 5HT receptor (5HT2-5HT7) subtypes. The vascular 5HT1 receptor is found predominantly in cranial blood vessels and mediates vasoconstriction.
In animals, sumatriptan selectively constricts the carotid arterial circulation, but does not alter cerebral blood flow. The carotid arterial circulation supplies blood to the extracranial and intracranial tissues such as the meninges, and dilatation and/or oedema formation in these vessels is thought to be the underlying mechanism of migraine in man. In addition, experimental evidence suggests that sumatriptan inhibits trigeminal nerve activity. Both these actions may contribute to the anti-migraine action of sumatriptan in humans.

Clinical trials.

Clinical studies conducted in the adult population.

Table 2 shows 1 and 2 hour efficacy results for two placebo-controlled trials of sumatriptan injection in 1,104 adult migraineurs with moderate or severe migraine pain.

5.2 Pharmacokinetic Properties

Absorption.

Following subcutaneous injection, sumatriptan has a high mean bioavailability (96%) with peak serum concentrations occurring in 25 minutes. Average peak serum concentration after a 6 mg subcutaneous dose is 72 nanogram/mL. After oral administration, sumatriptan is rapidly absorbed, 70% of maximum concentration occurring at 45 minutes. After a 100 mg dose the mean maximum plasma concentration is 54 nanogram/mL. Mean absolute oral bioavailability is 14% partly due to pre-systemic metabolism and partly due to incomplete absorption. Oral absorption of sumatriptan is not significantly affected by food.

Metabolism.

Sumatriptan is eliminated primarily by oxidative metabolism mediated by monoamine oxidase A. The major metabolite, the indole acetic acid analogue of sumatriptan, is mainly excreted in the urine, where it is present as a free acid and the glucuronide conjugate. It has no known 5HT1 or 5HT2 activity.
Minor metabolites have not been identified.

Excretion.

The elimination phase half-life is approximately 2 hours. Non-renal clearance accounts for about 80% of the total clearance. The major metabolite, the indole acetic acid analogue of sumatriptan, is mainly excreted in the urine.
The pharmacokinetics of oral or intranasal sumatriptan do not appear to be significantly affected by migraine attacks.
In a pilot study no significant differences were found in the pharmacokinetic parameters between elderly and young healthy volunteers.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for Injections, Sodium chloride.

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 25°C. Brief temperature excursions below and above 25°C permitted. Protect from light.

6.5 Nature and Contents of Container

Pre-filled pen (autoinjector) that contains 0.5 mL solution in a clear type 1 glass 1 mL syringe.
Needle shield made with natural rubber latex.
Clustran is packed in a box containing either one or two pre-filled pens.
Not all pack sizes may be marketed in Australia.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.


CAS number.

The CAS Registry number is 103628-48-4.
Sumatriptan is a white to off-white powder.
Chemically, sumatriptan succinate is: 3-[2-(dimethylamino) ethyl]-N-methyl-1H-indole-5-methane sulphonamide, butane-1,4-dioate (1:1).
The molecular formula of sumatriptan succinate is C14H21N3O2SC4H6O4.
The relative molecular mass is 413.5.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - S4 Prescription Medicine.

Summary Table of Changes