Consumer medicine information

What is in this leaflet

This leaflet answers some of the common questions people ask about ZOLTRIP. It does not contain all the information that is known about ZOLTRIP. It does not take the place of talking to your doctor or pharmacist.

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

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What ZOLTRIP is for

ZOLTRIP belongs to a group of medicines called serotonin agonists. These medicines are used to relieve migraine.

Migraine is thought to be caused by the widening of certain blood vessels in the brain. ZOLTRIP makes the blood vessels narrower to ease the migraine.

Some people have a warning stage called 'aura' before the migraine headache starts. Aura can include numbness in the face or down one arm, changes in mood, or problems with eyesight such as seeing blank spots or flashing lights.

ZOLTRIP can be used in migraine with or without aura. It should not be used to treat types of migraine called 'hemiplegic' or 'basilar' migraine.

ZOLTRIP does not work in headaches that are not migraine.

Your doctor will have explained why you are being treated with ZOLTRIP and told you what dose to take.

Follow all directions given to you by your doctor carefully. They may differ from the information contained in this leaflet.

Your doctor may prescribe this medicine for another use. Ask your doctor if you want more information.

ZOLTRIP is not addictive.

Before you take ZOLTRIP

When you must not take it

Do not use ZOLTRIP if you are pregnant or breastfeeding unless your doctor says so. The safety of taking this medicine when you are pregnant is unknown.

Do not give ZOLTRIP to children. There is no experience of its use in children under 12 years of age.

One study in children aged 12 to 17 years indicated no benefit with ZOLTRIP treatment.

Do not use ZOLTRIP after the use by (expiry) date printed on the pack. It may have no effect at all, or an unexpected effect, if you take it after the expiry date.

Do not use ZOLTRIP if the packaging is torn or shows signs of tampering.

Do not give this medicine to anyone else.

Before you start to use it

You must tell your doctor if:

1. you have any allergies to

• any ingredient listed at the end of this leaflet
• any other substances
  If you have an allergic reaction, you may get a skin rash, hayfever, difficulty breathing or feel faint.

2. you have or have had any of these medical conditions

• high blood pressure
• a feeling of tightness, pressure of heaviness in the chest
• a heart attack, other heart problems or a family history of heart problems
• a stroke or dizzy spells caused by lack of blood flow to the brain
• blood vessel problems that cause poor circulation in the arms or legs
• kidney or liver disease
• high cholesterol levels in the blood
• diabetes

It may not be safe for you to take ZOLTRIP if you have any of these conditions. Your doctor may decide to do tests to check if your heart is healthy before prescribing ZOLTRIP tablets.

Taking other medicines

Tell your doctor if you are taking any other medicines, including:

• other medicines for migraine, such as sumatriptan, naratriptan, ergotamine, dihydroergotamine or methysergide
• medicines for depression
• cimetidine for the treatment of indigestion or stomach ulcers
• antibiotics known as quinolones (eg noroxin).
• St John's Wort (Hypericum perforatum)
• any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

These medicines may affect the way ZOLTRIP works. Your doctor or pharmacist can tell you what to do if you are taking any other medicines.

If you have not told your doctor about any of these things, tell them before you take any ZOLTRIP.

Taking ZOLTRIP

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

How much to take

The usual dose is one tablet (2.5 mg) as soon as you feel the migraine headache start.

If your migraine is still present after two hours, or if it returns within 24 hours, you can take another tablet.

Do not take more than 10 mg (four 2.5 mg tablets) in twenty-four hours.

Swallow your ZOLTRIP tablets whole with a glass of water.

You can take them before or after food.

When to take it

You can take ZOLTRIP when you feel the headache start or after it has already begun.

ZOLTRIP tablets should only be taken to treat the migraine headache after it has started. They should not be used to prevent the migraine attacks from occurring.

Overdose

Immediately telephone your doctor or the Poisons Information Centre (13 11 26), or go to casualty at your nearest hospital if you think that you or anyone else may have taken too much ZOLTRIP even if there are no signs of discomfort or poisoning.

While you are taking ZOLTRIP

Things you must do

If you go into hospital tell the staff if you have taken any ZOLTRIP that day.

If you are about to start taking any other medicine, tell your doctor and pharmacist that you are taking ZOLTRIP.

Things you must not do

Do not give ZOLTRIP to anyone else, even if they have the same condition as you.

Do not use ZOLTRIP tablets to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how ZOLTRIP affects you. ZOLTRIP can make some people feel dizzy or sleepy. Make sure you know how you react to ZOLTRIP before you do anything that could be dangerous if you are dizzy or sleepy.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking ZOLTRIP.

ZOLTRIP helps most people with migraine, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

• increased feeling or sensitivity, especially in the skin
• feeling warm
• feelings of heaviness, tightness, pain or pressure in the throat, neck, arms or legs
• unusual tiredness or weakness
• aching muscles not caused by exercise
• dizziness
• nausea
• stomach pain
• vomiting
• headache
• palpitations (irregular heart beat)
• sleepiness
• dry mouth

These are all common and mild side effects of ZOLTRIP.

If any of the following happen, stop taking ZOLTRIP and tell your doctor immediately or go to the emergency department at your nearest hospital.

• wheezing, difficulty in breathing, swelling of the lips or mouth, a lumpy rash (hives) or fainting.
• a feeling of tightness, pressure or heaviness in the chest
• irregular heart beats/ increased heart rate
• numbness or loss of strength of the arms or legs, headache, dizziness, confusion, visual disturbance, difficulty swallowing, slurred speech or loss of speech
• bloody diarrhoea or prolonged stomach pain

These are serious side effects. If you have them, you may have had a serious reaction to ZOLTRIP. You may need urgent medical attention or hospitalisation. Serious side effects are rare.

Some people may get other side effects not listed above. Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

After using ZOLTRIP

Storage

Keep your tablets in the blister pack until it is time to take them. If you take ZOLTRIP out of the blister pack it will not keep well.

Keep it in a cool dry place where the temperature stays below 25°C.

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

Keep it where young 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

Ask your pharmacist what to do with any tablets you have left over if your doctor tells you to stop taking them, or you find that the expiry date has passed.

Product description

What ZOLTRIP looks like

ZOLTRIP 2.5 mg are light pink, round, film-coated tablets, debossed with ‘2.5’ on one side and plain on the other. ZOLTRIP 2.5 mg tablets are presented in blister packs containing 2 tablets.

Ingredients

Each tablet contains 2.5 mg zolmitriptan as the active ingredient plus the following inactive (excipient) ingredients:

• microcrystalline cellulose
• lactose
• sodium starch glycollate type A
• magnesium stearate
• Opadry Pink 02G84574 (hypromellose, titanium dioxide, macrogol 400, macrogol 8000, iron oxide red)

Contains sugars as lactose. Gluten free.

Sponsor

Arrotex Pharmaceuticals Pty Ltd
15 – 17 Chapel Street
Cremorne VIC 3121

Australian registration number:
AUST R 200877

This leaflet was prepared in March 2023.

Published by MIMS April 2023

1 Name of Medicine

Zolmitriptan.

2 Qualitative and Quantitative Composition

Zolmitriptan is a white to almost white powder slightly soluble in water (1.3 mg/mL at 250°C) but shows greater solubility in 0.1 M hydrochloric acid. Zolmitriptan has a pKa of 9.6. Zolmitriptan is a chiral molecule, which is synthesised as the S-enantiomer.
Zoltrip tablets contain 2.5 mg of zolmitriptan.

Excipients of known effect.

3 Pharmaceutical Form

Zoltrip.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

The recommended initial dose of zolmitriptan to treat a migraine attack is 2.5 mg.
Zoltrip tablet should be swallowed whole with water.
If symptoms of migraine persist or recur within 24 hours of an initial response, a second dose may be taken. If a second dose is required, it should not be taken within 2 hours of the initial dose.
If a patient does not achieve satisfactory relief with 2.5 mg doses, subsequent attacks can be treated with 5 mg doses of zolmitriptan.
The onset of action in responders is apparent within 1 hour of dosing.
Zolmitriptan is equally effective whenever the tablets are taken during a migraine attack; although it is advisable that tablets are taken as early as possible after the onset of migraine headache.
In the event of recurrent attacks, it is recommended that the total intake of zolmitriptan, in a 24 hour period, should not exceed 10 mg.
Zolmitriptan is not indicated for prophylaxis of migraine.

Patient subgroups.

Children.

Adults including the elderly.

Use in adults with hepatic impairment.

Use in adults with renal impairment.

4.3 Contraindications

Zoltrip is contraindicated in the following cases:
Hypersensitivity to any component of the product.
A history of myocardial infarction.
Ischaemic heart disease; Prinzmetal angina/ coronary vasospasm; peripheral vascular disease; symptoms or signs consistent with ischaemic heart disease.
Moderate or severe hypertension and mild uncontrolled hypertension.
Ergotamine or ergotamine derivatives should not be used concomitantly with zolmitriptan.
Other 5HT_1D receptor agonists should not be used concomitantly with zolmitriptan.
Creatinine clearance of less than 15 mL/min.
On theoretical grounds (see Section 5.1 Pharmacodynamic Properties), zolmitriptan should not be administered to patients with a history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

4.4 Special Warnings and Precautions for Use

Cerebrovascular events have been reported in patients treated with 5HT₁ agonists, some resulting in fatalities. In a number of cases, it appears that the cerebrovascular events were primary, the agonist having been administered in the incorrect belief that the symptoms were a consequence of the migraine. Zolmitriptan should only be used when a clear diagnosis of migraine has been established. Care should be taken to exclude other potentially serious neurological conditions. There are no data on the use of zolmitriptan in hemiplegic or basilar migraine.
Migraneurs may be at risk of certain cerebrovascular events. Cerebral haemorrhage, subarachnoid haemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with 5HT₁ agonists.
There have been rare reports of anaphylaxis/ anaphylactoid reactions in patients receiving zolmitriptan.
Zolmitriptan should not be given to patients with symptomatic Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathways.
This class of compounds (5HT_1B/1D agonists) has been associated with coronary vasospasm, angina pectoris and myocardial infarction. In very rare cases this has occurred with zolmitriptan. In patients with risk factors for ischaemic heart disease, cardiovascular evaluation prior to commencement of treatment with this class of compounds, including zolmitriptan, is recommended (see Section 4.3 Contraindications). These evaluations, however, 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.
As with other 5HT_1D agonists, atypical sensations over the precordium (see Section 4.8 Adverse Effects (Undesirable Effects)) have been reported after the administration of zolmitriptan. Where such symptoms are thought to indicate ischaemic heart disease, no further doses of zolmitriptan should be given and appropriate evaluation carried out.
Serotonin syndrome has been reported with combined use of triptans, and selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Serotonin syndrome is a potentially life threatening condition, and it may include signs and symptoms such as: mental status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyper-reflexia, incoordination, weakness), and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea).
In accordance with the Hunter Criteria, diagnosis is likely when (in presence of a serotonergic agent) one of the following is observed: spontaneous clonus; inducible or ocular clonus with agitation or diaphoresis; tremor and hyperreflexia; hypertonia and body temperature > 38°C and inducible or ocular clonus.
Careful observation of the patient is advised when zolmitriptan is administered with an SSRI or SNRI, particularly during treatment initiation and dosage increases (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Withdrawal of the serotonergic medicines usually brings about an improvement. Treatment depends on the type and severity of the symptoms.
Overuse of acute migraine medications may lead to exacerbations 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 medications, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
Transient increases in systemic blood pressure have been reported in patients with and without a history of hypertension; very rarely these increases in blood pressure have been associated with significant clinical events.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There is no evidence that concomitant use of migraine prophylactic medications has any effect on the efficacy or unwanted effects of zolmitriptan (for example beta-blockers, oral dihydroergotamine, pizotifen).
The pharmacokinetics and tolerability of zolmitriptan were unaffected by acute symptomatic treatments such as paracetamol, metoclopramide and ergotamine. Concomitant administration of other 5HT_1D agonists within 24 hours of zolmitriptan treatment should be avoided.
Data from healthy subjects suggest there are no pharmacokinetic or clinically significant interactions between zolmitriptan and ergotamine. However, the increased risk of coronary vasospasm is a theoretical possibility, and concomitant administration is contraindicated. It is advised to wait at least 24 hours following the use of ergotamine containing preparations before administering zolmitriptan. Conversely it is advised to wait at least six hours following use of zolmitriptan before administering an ergotamine containing product.
The major metabolite of zolmitriptan, the indole acetic acid (2161W92), is derived from the active metabolite, N-desmethyl zolmitriptan (183C91), by the action of monoamine oxidase A. This is evidenced by the effects of coadministration of the selective MAO-A inhibitor, moclobemide, which resulted in a 3-fold increase in the exposure to 183C91 but had minimal effects (increase of 26% in AUC) on zolmitriptan levels. (The metabolite 183C91 is also a 5HT_1D agonist with higher receptor affinity than the parent drug and therefore contributes to the overall effect after zolmitriptan administration). Hence, in patients taking a MAO-A inhibitor (selective or nonselective), a maximum intake of 5 mg zolmitriptan in 24 hours is recommended.
Following the administration of cimetidine, a general P450 inhibitor, the half-life of zolmitriptan was increased by 44% and the AUC increased by 48%. In addition, the half-life and AUC of the active, N-desmethylated, metabolite (183C91) were doubled. A maximum dose of 5 mg zolmitriptan in 24 hours is recommended in patients taking cimetidine. Based on the overall interaction profile, an interaction with inhibitors of the cytochrome P450 isoenzyme CYP1A2 cannot be excluded. Therefore, the same dosage reduction is recommended with compounds of this type, such as fluvoxamine and the quinolone antibiotics (e.g. ciprofloxacin). Following the administration of rifampicin, no clinically relevant differences in the pharmacokinetics of zolmitriptan or its active metabolite were observed.
Cases of life threatening syndrome have been reported during combined use of triptans, and SSRIs (e.g. fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g. venlafaxine) (see Section 4.4 Special Warnings and Precautions for Use).
As with other 5HT_1B/1D agonists, there is a potential pharmacodynamic interaction with the herbal remedy, St. John's wort (Hypericum perforatum) which may result in an increase in undesirable effects.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Even though there was no significant impairment of psychomotor test performances in healthy volunteers following doses of up to 20 mg, somnolence was reported in pharmacological and clinical trials. Caution is recommended in patients performing skilled tasks (e.g. driving or operating machinery) as drowsiness and other symptoms may occur during a migraine attack and following treatment.

4.8 Adverse Effects (Undesirable Effects)

Zolmitriptan is well tolerated. Adverse reactions are typically mild/ moderate, transient, not serious and resolve spontaneously without additional treatment. The adverse event profile has been demonstrated to be similar for the administration of either 2.5 mg or 5 mg of zolmitriptan.
Possible adverse reactions tend to occur within four hours of dosing and are no more frequent following repeated dosing; certain symptoms may be considered to be part of the migraine attack itself.

Clinical trial data.

Atypical sensation.

General.

Cardiovascular.

Digestive.

Haemic.

Metabolic.

Musculoskeletal.

Neurological.

Respiratory.

Skin.

Special senses.

Urogenital.

Postmarketing data.

Reporting suspected adverse effects.

4.9 Overdose

Volunteers receiving single oral doses of 50 mg commonly experienced sedation.
The elimination half-life of zolmitriptan tablets is 2.5 to 3 hours, (see Section 5.2 Pharmacokinetic Properties) and therefore monitoring of patients after overdose with zolmitriptan tablets should continue for at least 15 hours or while symptoms or signs persist.
There is no specific antidote to zolmitriptan. In cases of severe intoxication, intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system.
It is unknown what effect haemodialysis or peritoneal dialysis has on the serum concentrations of zolmitriptan.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

Treatment of acute migraine, with or without aura, with zolmitriptan tablets.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

Special populations.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets contain microcrystalline cellulose, lactose monohydrate, sodium starch glycollate type A, magnesium stearate and Opadry Pink 02G84574 (hypromellose, titanium dioxide, macrogol 400, macrogol 8000, iron oxide red). The tablets are gluten free.

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.

6.5 Nature and Contents of Container

Zoltrip.

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

Zolmitriptan.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicines - S4.

Summary Table of Changes