SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

[Film-coated tablets only] [Invented name] 2.5 mg film-coated tablets

[Orodispersible tablets only] [Invented name] 2.5 mg orodispersible tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

[Film-coated tablets only] Each film-coated tablet contains 2.5 mg zolmitriptan.

[Orodispersible tablets only] Each orodispersible tablet contains 2.5 mg zolmitriptan. Excipient with known effect: Each tablet contains 2.5 mg aspartame (E951).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

[Film-coated tablets only] Film-coated tablet Yellow, round shaped, biconvex film coated tablets of 7.5 ± 0.3 mm diameter and with ‘2.5’ debossed on one side and plain on other side.

[Orodispersible tablets only] Orodispersible tablet White to off-white, round, flat faced beveled edge uncoated tablet of 6.4 ± 0.3 mm diameter and with ‘2.5’ debossed on one side and plain on other side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

[Invented name] is indicated for the acute treatment of headache with or without aura. [Invented name] is not indicated for prophylaxis of migraine.

4.2 Posology and method of administration

Posology: The recommended dose is 2.5 mg zolmitriptan. It is advisable that [Invented name] is taken as early as possible after the onset of migraine headache but it is also effective if taken at a later stage.

If symptoms of migraine should recur within 24 hours following 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 respond to the first dose, it is unlikely that a second dose will be of benefit in the same attack.

If a patient does not achieve satisfactory relief with 2.5 mg zolmitriptan, for subsequent attacks doses of 5 mg zolmitriptan could be considered. The total daily intake should not exceed 10 mg. Not more than 2 doses should be taken in any 24 hour period.

Special populations:

Patients aged over 65 years Safety and efficacy of [Invented name] in patients aged over 65 years have not been established. Use of [Invented name] in the elderly is therefore not recommended.

Patients with hepatic impairment Metabolism of zolmitriptan is reduced in patients with hepatic impairment (see section 5.2). For patients with moderate or severe hepatic impairment a maximum dose of 5 mg zolmitriptan in 24 hours is recommended. However, no dose adjustment is required for patients with mild hepatic impairment.

Patients with renal impairment No dosage adjustment required in patients with a creatinine clearance of more than 15 ml/min (see sections 4.3 and 5.2).

Interactions requiring dose adjustment (see section 4.5) For patients taking MAO-A inhibitors, a maximum dose of 5 mg in 24 hours is recommended. A maximum dose of 5 mg zolmitriptan in 24 hours is recommended in patients taking .

A maximum dose of 5 mg zolmitriptan in 24 hours is recommended in patients taking specific inhibitors of CYP 1A2 such as fluvoxamine and the quinolones (e.g. ciprofloxacin).

Children (under 12 years of age) Safety and efficacy of zolmitriptan in children have not been evaluated. Use of [Invented name] in children is therefore not recommended.

Adolescents (12 - 17 years of age) The efficacy of zolmitriptan was not demonstrated in a placebo controlled clinical trial for patients aged 12 to 17 years. Use of [Invented name] tablets in adolescents is therefore not recommended.

Method of administration: [Film-coated tablets only] [Invented name] should be swallowed whole and with a drink of water.

[Orodispersible tablets only] The orodispersible tablet need not be taken with liquid; the orodispersible tablet rapidly dissolves when placed on the tongue and swallowed with the patient's saliva. The orodispersible tablet can be used in situations in which liquids are not available. Orodispersible tablets may also be beneficial for patients who suffer from nausea and are unable to drink during a migraine attack, or for patients who do not like swallowing conventional tablets. However, a delay in the absorption of zolmitriptan from orodispersible tablets can occur which may delay the onset of action.

4.3 Contraindications

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  Moderate or severe hypertension, and mild uncontrolled hypertension.  A history of myocardial infarction or ischaemic heart disease.  Coronary vasospasm/Prinzmetal's angina.  Peripheral vascular disease.  A history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA).  Concomitant administration of zolmitriptan with or ergotamine derivatives (including ) or other 5-HT1 receptor agonists (e.g. , ).  Creatinine clearance lower than 15 ml/min.

4.4 Special warnings and precautions for use

[Invented name] should only be used where a clear diagnosis of migraine has been established. As with other acute migraine therapies, 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. [Invented name] is not indicated for use in hemiplegic, basilar or ophthalmophlegic 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 5HT1B/1D agonists.

Zolmitriptan should not be given to patients with symptomatic Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathways.

In very rare cases, as with other 5-HT1B/1D agonists, coronary vasospasm, angina pectoris and myocardial infarction have been reported. [Invented name] should not be given to patients with risk factors for ischaemic heart disease (e.g. smoking, hypertension, hyperlipidaemia, diabetes mellitus, heredity) without prior cardiovascular evaluation (see section 4.3). Special consideration should be given to postmenopausal women and males over 40 with these risk factors. 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 5-HT1B/1D agonists, heaviness, pressure or tightness over the precordium (see section 4.8) have been reported after the administration of zolmitriptan. If chest pain or symptoms consistent with ischaemic heart disease occur, no further doses of zolmitriptan should be taken until after appropriate medical evaluation has been carried out.

As with other 5-HT1B/1D agonists 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. The dose recommendation for zolmitriptan should not be exceeded.

As with other 5-HT1B/1D agonists, there have been rare reports of anaphylaxis/anaphylactoid reactions in patients receiving zolmitriptan.

Prolonged use of any type of painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The diagnosis of medication overuse headache should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.

Serotonin Syndrome has been reported with combined use of , and Selective Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine 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. hyperreflexia, in-coordination), and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Careful observation of the patient is advised, if concomitant treatment with zolmitriptan and an SSRI or SNRI is clinically warranted, particularly during treatment initiation and dosage increases (see section 4.5).

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John’s wort (Hypericum perforatum).

Zolmitriptan, when administered as conventional oral tablets, if taken during the aura, has not been demonstrated to prevent the migraine headache and therefore [Invented name] should be taken during the headache phase of migraine.

[Orodispersible tablets only]: [Invented name] contains aspartame (E951). Aspartam contains a source of phenylalanine. May be harmful for people with phenylketonuria.

4.5. Interaction with other medicinal products and other forms of interactions

Interaction studies were performed with caffeine, ergotamine, , , , , , rifampicin and and no clinically relevant differences in the of zolmitriptan or its active metabolite were observed.

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. Therefore, 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 any ergotamine containing preparation (see section 4.3).

Following administration of , a specific MAO-A inhibitor, there was a small increase (26%) in AUC for zolmitriptan and a 3-fold increase in AUC of the active metabolite. Therefore, a maximum intake of 5 mg zolmitriptan in 24 hours is recommended in patients taking a MAO-A inhibitor. The medicinal products should not be used together if doses of moclobemide higher than 150 mg b.i.d. are administered.

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).

Selegiline (a MAO-B inhibitor) and fluoxetine (a selective serotonin reuptake inhibitor, SSRI) did not result in any pharmacokinetic interaction with zolmitriptan. However, there have been isolated reports describing patients with symptoms compatible with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans (see section 4.4).

As with other 5-HT1B/1D receptor agonists, zolmitriptan could delay the absorption of other medicinal products. Concomitant administration of other 5-HT1B/1D agonists within 24 hours of zolmitriptan treatment should be avoided. Similarly, administration of zolmitriptan within 24 hours of the use of other 5-HT1B/1D agonists should be avoided.

As with other 5HTIB/ID agonists, there is the potential for dynamic interactions 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

Pregnancy The safety of this medical product for use in human pregnancy has not been established. Evaluation of experimental animal studies does not indicate direct teratogenic effects. However, some findings in embryotoxicity studies suggested impaired embryo viability. Administration of zolmitriptan should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

Lactation Studies have shown that zolmitriptan passes into the milk of lactating animals. No data exist for passage of zolmitriptan into human breast milk. Therefore, caution should be exercised when administering [Invented name] to women who are breast-feeding. Infant exposure should be minimised by avoiding breast feeding for 24 hours after treatment.

Fertility There are no data indicating that zolmitriptan may affect fertility.

4.7 Effects on ability to drive and use machines

[Invented name] has no or negligible influence on the ability to drive and use machines. There was no significant impairment of performance of psychomotor tests with doses up to 20 mg zolmitriptan in a small group of healthy individuals. 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.

4.8 Undesirable effects

Possible adverse reactions are typically transient, tend to occur within 4 hours of dosing, are no more frequent following repeated dosing and resolve spontaneously without additional treatment.

The following definitions apply to the incidence of the undesirable effects: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

System organ Frequency Undesirable effects class Immune system Rare Anaphylaxis/Anaphylactoid Reactions disorders Hypersensitivity reactions including urticaria, angioedema Nervous system Common Abnormalities or disturbances of sensation disorders Dizziness Headache Hyperaesthesia Paraesthesia Somnolence Warm sensation Cardiac disorders Common Palpitations

Uncommon Tachycardia

Very rare Angina pectoris Coronary vasospasm Myocardial infarction Vascular disorders Uncommon Slight increases in blood pressure Transient increases in systemic blood pressure Gastrointestinal Common Abdominal pain disorders Dry mouth Nausea Vomiting Dysphagia Very rare Gastrointestinal infarction or necrosis Gastrointestinal ischaemic events which may present as bloody diarrhoea or abdominal pain Ischaemic colitis Splenic Infarction Musculoskeletal Common Muscle weakness and connective Myalgia tissue disorders Renal and urinary Uncommon Polyuria disorders Increased urinary frequency Very rare Urinary urgency

General disorders Common Asthenia and administration Heaviness, tightness, pain or pressure in site conditions throat, neck limbs or chest

Certain symptoms may be part of the migraine attack itself.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

4.9 Overdose

Volunteers receiving single oral doses of 50 mg commonly experienced sedation.

The elimination half-life of zolmitriptan is 2.5 to 3 hours, (see section 5.2) and therefore monitoring of patients after overdose with [Invented name] 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.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics; antimigraine preparations; Selective serotonin (5HT1) agonists ATC code: N02CC03

Zolmitriptan has been demonstrated to be a selective agonist for the vascular human recombinant 5-HT1B and 5-HT1D receptor subtypes. Zolmitriptan is a high affinity 5-HT1B/1D receptor agonist with modest affinity for 5-HT1A receptors. Zolmitriptan has no significant affinity (as measured by radioligand binding assays) or pharmacological activity at other 5- HT receptors subtypes (5-HT2, 5-HT3, 5-HT4), or adrenergic, histaminic, muscarinic or dopaminergic receptors. In animal models, the administration of zolmitriptan causes vasoconstriction in the carotid arterial circulation. In addition, experimental studies in animals suggest that zolmitriptan inhibits central and peripheral trigeminal nerve activity with inhibition of neuropeptide release (calcitonin gene related peptide (CGRP), vasoactive intestinal peptide (VIP) and Substance P).

In clinical studies with zolmitriptan conventional tablets the onset of efficacy is apparent from one hour, with increasing efficacy being noted between 2 and 4 hours on headache and other symptoms of migraine such as nausea, photophobia and phonophobia.

Zolmitriptan, when administered as conventional oral tablets, is consistently effective in migraine with or without aura and in menstrually associated migraine. Zolmitriptan, when administered as conventional oral tablets, if taken during the aura, has not been demonstrated to prevent the migraine headache and therefore [Invented name] should be taken during the headache phase of migraine.

One controlled clinical trial in 696 adolescents with migraine failed to demonstrate superiority of zolmitriptan tablets at doses of 2.5 mg, 5 mg and 10 mg over placebo. Efficacy was not demonstrated.

5.2 Pharmacokinetic properties

Following oral administration of zolmitriptan conventional tablets zolmitriptan is rapidly and well absorbed (at least 64%) after oral administration to man. The mean absolute of the parent compound is approximately 40%. There is an active metabolite (183C91, the N-desmethyl metabolite) which is also a 5-HTIB/1D receptor agonist and is 2 to 6 times as potent, in animal models, as zolmitriptan.

In healthy subjects, when given as a single dose, zolmitriptan and its active metabolite the N-desmethyl metabolite, display dose-proportional AUC and Cmax over the dose range 2.5 to 50 mg. Absorption of zolmitriptan is rapid in healthy volunteers, 75% of Cmax is achieved within 1 hour and after this the concentration of zolmitriptan in plasma is maintained at approximately this level until 4 to 5 hours after dosing. Zolmitriptan absorption is unaffected by the presence of food. There is no evidence of accumulation on multiple dosing of zolmitriptan. Plasma concentration of zolmitriptan and its metabolites are lower in the first 4 hours after drug administration during a migraine compared with a migraine-free period, suggesting delayed absorption consistent with the reduced rate of gastric emptying observed during a migraine attack.

Zolmitriptan is eliminated largely by hepatic biotransformation followed by urinary of the metabolites. There are three major metabolites: the indole acetic acid, (the major metabolite in plasma and urine), the N-oxide and N-desmethyl analogues. The N- desmethylated metabolite is active whilst the others are not. Plasma concentrations of the N- desmethylated metabolite are approximately half those of the parent drug, hence it would therefore be expected to contribute to the therapeutic action of zolmitriptan. Over 60% of a single oral dose is excreted in the urine (mainly as the indole acetic acid metabolite) and about 30% in faeces, mainly as unchanged parent compound.

A study to evaluate the effect of hepatic impairment on the pharmacokinetics of zolmitriptan showed that the AUC and Cmax were increased by 94% and 50% respectively in patients with moderate hepatic impairment and by 226% and 47% respectively in patients with severe hepatic impairment compared with healthy volunteers. Exposure to the metabolites, including the active metabolite, was decreased. For the active metabolite 183C91 metabolite, AUC and Cmax were reduced by 33% and 44% respectively in patients with moderate hepatic impairment and by 82% and 90% respectively in patients with severe hepatic impairment.

The plasma half-life (t½) of zolmitriptan was 4.7 hours in healthy volunteers, 7.3 hours in patients with moderate hepatic impairment and 12 hours in those with severe liver disease. The corresponding t½ values for the 183C91 metabolite were 5.7 hours, 7.5 hours and 7.8 hours respectively.

Following intravenous administration, the mean total plasma clearance is approximately 10 ml/min/kg, of which one quarter is renal clearance. Renal clearance is greater than glomerular filtration rate suggesting renal tubular secretion. The volume of distribution following intravenous administration is 2.4 L/kg. Plasma protein binding of zolmitriptan and the N- desmethyl metabolite is low (approximately 25%). The mean elimination half-life of zolmitriptan is 2.5 to 3 hours. The half-lives of its metabolites are similar, suggesting their elimination is formation-rate limited.

Renal clearance of zolmitriptan and all its metabolites is reduced (7 to 8 fold) in patients with moderate to severe renal impairment compared to healthy subjects, although the AUC of the parent compound and the active metabolite were only slightly higher (16 and 35% respectively) with a 1 hour increase in half-life to 3 to 3.5 hours. These parameters are within the ranges seen in healthy volunteers.

The pharmacokinetics of zolmitriptan in healthy elderly subjects was similar to those in healthy young volunteers.

[Orodispersible tablets only] Zolmitriptan orodispersible tablets were demonstrated to be bioequivalent with the conventional tablet in terms of AUC and Cmax for zolmitriptan and its active metabolite 183C91. Clinical pharmacology data show that the tmax for zolmitriptan can be later for the orally dispersible tablet (range 0.6 to 5h, median 3h) compared to the conventional tablet (range 0.5 to 3h, median 1.5h). The tmax for the active metabolite was similar for both formulations (median 3h).

5.3. Preclinical safety data

Preclinical effects in single and repeat dose toxicity studies were observed only at exposures well in excess of the maximum human exposure.

The findings from in vitro and in vivo genetic toxicity studies show that genotoxic effects of zolmitriptan are not to be expected under the conditions of clinical use.

No tumours relevant to the clinical use were found in mouse and rat carcinogenicity studies.

As with other 5HT1B/1D receptor agonists, zolmitriptan binds to melanin.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

[Film-coated tablets only]: Tablet core: Mannitol (E421) Cellulose Microcrystalline Croscarmellose sodium Sillica Colloidal Anhydrous Magnesium stearate (E470b)

Tablet coating: Hypromellose (E 464) Titanium Dioxide (E 171) Macrogol 400 Macrogol 8000 Iron oxide yellow (E 172)

[Orodispersible tablets only]: Mannitol (E421) Cellulose Microcrystalline Aspartame (E951) Croscarmellose sodium Sillica Colloidal Anhydrous Magnesium stearate (E470b) Orange flavour (containing nature-identical flavouring substance(s), flavouring preparation, natural flavouring substance(s), maltodextrin (Maize), arabic gum (acacia gum) (E414), ascorbic acid (E300) and butylated hydroxyanisole (E320)).

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from moisture.

6.5 Nature and content of container

[Invented name] is supplied in OPA/Al/PVC/Al blisters.

[Film-coated tablets only] Size of packing: 2 film-coated tablets DE/H/3747/001-002/DC Size of packing: 2, 3 and 6 film-coated tablets

[Orodispersible tablets only] Size of packing: 2 orodispersible tablets DE/H/3747/001-002/DC Size of packing: 2 and 6 orodispersible tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10. DATE OF REVISION OF THE TEXT

[To be completed nationally]

LABELLING PARTICULARS TO APPEAR ON THE OUTER PACKAGING

1. NAME OF THE MEDICINAL PRODUCT

[Film-coated tablets only] [Invented name] 2.5 mg film-coated tablets

[Orodispersible tablets only] [Invented name] 2.5 mg orodispersible tablets Zolmitriptan

2. STATEMENT OF ACTIVE SUBSTANCE(S)

[Film-coated tablets only] Each film-coated tablet contains 2.5 mg zolmitriptan.

[Orodispersible tablets only] Each orodispersible tablet contains 2.5 mg zolmitriptan.

3. LIST OF EXCIPIENTS

[Orodispersible tablets only] Contains aspartame (E951). See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

[Film-coated tablets only] Film-coated tablet 2 film-coated tablets DE/H/3747/001-002/DC 2 film-coated tablets 3 film-coated tablets 6 film-coated tablets

[Orodispersible tablets only] Orodispersible tablet 2 orodispersible tablets DE/H/3747/001-002/DC 2 orodispersible tablets 6 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use. Read the package leaflet before use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP:

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

12. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

13. BATCH NUMBER

Batch:

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

[Film-coated tablets only] [Invented name] 2.5 mg film-coated tablets

[Orodispersible tablets only] [Invented name] 2.5 mg orodispersible tablets MINIMUM PARTICULARS TO APPEAR ON BLISTER

1. NAME OF THE MEDICINAL PRODUCT

[Film-coated tablets only] [Invented name] 2.5 mg film-coated tablets

[Orodispersible tablets only] [Invented name] 2.5 mg orodispersible tablets Zolmitriptan

2. NAME OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

3. EXPIRY DATE

EXP:

4. BATCH NUMBER

Batch:

5. OTHER Package leaflet: information for the user

[Film-coated tablets only] [Invented name] 2.5 mg film-coated tablets

[Orodispersible tablets only] [Invented name] 2.5 mg orodispersible tablets

Zolmitriptan

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet: 1. What [Invented name] is and what it is used for 2. What you need to know before you take [Invented name] 3. How to take [Invented name] 4. Possible side effects 5. How to store [Invented name] 6. Contents of the pack and other information

1. What [Invented name] is and what it is used for

[Invented name] contains active substance zolmitriptan and belongs to a group of medicines called triptans.

[Invented name] is used to treat migraine attacks (headache and nausea).

Migraine symptoms may be caused by swollen blood vessels in the head. [Invented name] reduces the widening of these blood vessels. This helps to take away the headache and other symptoms of a migraine attack, such as feeling or being sick (nausea or vomiting) and being sensitive to light and sound. [Invented name] works only when a migraine attack has started. It will not stop you from getting an attack.

2. What you need to know before you take [Invented name]

Do not take [Invented name] if you  are allergic to zolmitriptan or any of the other ingredients of this medicine (listed in section 6).  have high blood pressure.  have ever had heart problems, including a heart attack, angina (chest pain caused by exercise or effort), Prinzmetal's angina (chest pain which happens at rest) or have experienced heart related symptoms such as shortness of breath or pressure over the chest.  have circulatory problem (restricted blood flow in your legs or arms).  have had a stroke or short-lasting symptoms similar to stroke (transient ischaemic attack or TIA).  have severe kidney problem.  are at the same time taking some other medicines for migraine; e.g. ergotamine or ergot- type medicines like dihydroergotamine and methysergide or other medicines (see section below: 'Other medicines and [Invented name]').

Do not take [Invented name] if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking [Invented name].

Warnings and precautions Talk to your doctor or pharmacist before taking [Invented name] if you:  are at risk of getting ischaemic heart disease (poor blood flow in the arteries of the heart). Your risk is greater if you smoke, have high blood pressure, high levels of cholesterol, diabetes or if anyone in your family has ischaemic heart disease.  have ever had liver problems.  have headaches which are not like your usual migraine headache.  have been told that you have Wolff-Parkinson-White Syndrome (a type of abnormal heart beat).  are taking any medicine for treatment of depression or herbal remedy called St. John’s wort (see section below: 'Other medicines and [Invented name]').

[Invented name] is not recommended for patients under 18 years or over 65.

As with other migraine treatments, using too much [Invented name] can cause daily headaches or can make your migraine headaches worse. Ask your doctor if you think that this is the case for you. You may need to stop taking [Invented name] to correct the problem.

Other medicines and [Invented name] Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor if you are taking any of the following medicines:  Medicines for migraine - If you take a triptan other than [Invented name] (such as sumatriptan or naratriptan) leave 24 hours before taking [Invented name]. - After taking [Invented name] leave 24 hours before taking another triptan. - If you take medicines containing ergotamine or ergot-type medicines (such as dihydroergotamine or methysergide), leave 24 hours before taking [Invented name]. - After taking [Invented name] leave 6 hours before taking ergotamine or ergot-type medicines.  Medicines for depression - Mono-Amine Oxidase Inhibitors, also known as MAOIs (such as moclobemide). - SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine or sertraline. - SNRIs (serotonin norepinephrine reuptake inhibitors) such as venlafaxine or duloxetine.  Other medicines - Cimetidine (for indigestion or stomach ulcers). - A quinolone antibiotic (such as ciprofloxacin). - You should not take the herbal remedy St. John's wort (Hypericum perforatum) at the same time as this medicine because side effects of [Invented name] may be more likely to happen. If you already take a St. John's wort preparation, stop taking it and mention this to your doctor at your next visit.

[Invented name] with food and drink You can take [Invented name] with or without food. It does not affect the way that [Invented name] works.

Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or for advice before taking this medicine. It is not known if taking [Invented name] during pregnancy is harmful. Therefore it should be used during the pregnancy only if the potential benefit to the mother outweighs the potential risk to the unborn child and no other appropriate treatment option is available. No data exist on the excretion of zolmitriptan into breast milk. Therefore, as a precautionary measure, breast-feeding should be avoided for 24 hours after treatment.

Driving and using machines During a migraine attack your reactions may be slower than usual. Bear this in mind when you drive or use any tools or machines. [Invented name] is unlikely to affect driving or using tools or machines. However, it may make you feel sleepy. Wait to see how [Invented name] affects you before you try these activities.

[Orodispersible tablets only] [Invented name] contains aspartame Aspartame (951) contains a source of phenylalanine. May be harmful for people with phenylketonuria.

3. How to take [Invented name]

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

[Invented name] is used to treat migraine attacks. Take [Invented name] as soon as possible after your migraine headache has started. You can also take it once an attack is underway. Do not use it to prevent an attack.

How much to take Do not use more than the dose prescribed for you.

Adults (aged over 18 years and under 65 years) The usual starting dose is 2.5 mg zolmitriptan. If 2.5 mg zolmitriptan did not give you enough help with your migraine, tell your doctor. Your doctor may change your treatment and recommend you 5 mg zolmitriptan for next attack. Occurrence of side effects is more likely with higher doses. The maximum daily dose is 10 mg zolmitriptan.

Special patient groups Patients aged over 65 years [Invented name] should not be given to patients over 65 years. Patients with liver problems If you have liver problems, the recommended maximum daily dose is lowered to 5 mg. Patients with kidney problems Your dosage can be the same as in adults.

Children and adolescents under 18 years of age [Invented name] should not be given to children or adolescents under 18 years of age.

Taking this medicine [Film-coated tablets only]  Oral use.  Swallow your tablet with a drink of water.  You can take [Invented name] with or without food. It does not affect the way that [Invented name] works.

[Orodispersible tablets only]  Oral use  Place the tablet on your tongue, where it will dissolve and be swallowed with the saliva. You do not have to take a drink of water in order to swallow your tablet.  You can take [Invented name] with or without food. It does not affect the way that [Invented name] works.

If after 2 hours after taking [Invented name] you still have migraine or migraine returns within 24 hours You can take another dose if the migraine is still present after two hours or if it returns within 24 hours.

Do not take more than 2 doses of [Invented name] in a 24-hour period. Always wait at least 2 hours between doses.

If [invented name] did not give you enough help with your migraine, tell your doctor. Your doctor may change your treatment. If your condition worsens, seek medical attention.

If you take more [Invented name] than you should If you take more than you should or someone accidentally swallows some, contact your doctor or go to the nearest hospital straight away. Take the medicine pack and any remaining tablets with you so that the doctor knows what has been taken.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of the symptoms below could be part of the migraine attack itself.

If you experience any of the side effects listed below stop taking the medication and seek the doctor immediately  Rare: may affect up to 1 in 1,000 people - Allergic reactions including itchy rash (urticaria) and swelling of the face, lips, mouth, tongue and throat.  Very rare: may affect up to 1 in 10,000 people - Angina (pain in the chest, often brought on by exercise), heart attack or spasm of the blood vessels of the heart. The signs include chest pain and shortness of breath. - Spasm of the blood vessels of the gut, which can cause damage to your gut. The signs include stomach pain or bloody diarrhoea. - Bleeding in the brain (cerebral bleeding) or stroke.

In the course of the treatment with active substance of the product [Invented name] following adverse effects have also been observed  Common: may affect up to 1 in 10 people These side effects are usually mild and go away after a short time. - Abnormal sensations such as tingling in your fingers and toes or skin that is sensitive to touch. - Feeling sleepy, dizzy or warm. - Headache. - Uneven heartbeat. - Feeling sick (nausea) or being sick (vomiting). - Stomach pain. - Dry mouth. - Muscle weakness or muscle pain. - Feeling weak. - Heaviness, tightness, pain or pressure in the throat, neck, arms and legs, or chest. - Difficulty in swallowing.  Uncommon: may affect up to 1 in 100 people - Very fast heartbeat. - Slightly higher blood pressure. - Increase in the amount of water you pass (urine) or in how often you need to pass water.

Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report any side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store [Invented name]

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the package. The expiry date refers to the last day of that month. This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from moisture. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What [Invented name] contains [Film-coated tablets only] The active substance is zolmitriptan. Each film-coated tablet contains 2.5 mg zolmitriptan. The other ingredients are Tablet core: mannitol (E421), cellulose microcrystalline, croscarmellose sodium, sillica colloidal anhydrous, magnesium stearate (E470b) Tablet coating: hypromellose (E464), titanium dioxide (E171), macrogol 400, macrogol 8000, iron oxide yellow (E172).

[Orodispersible tablets only] The active substance is zolmitriptan. Each orodispersible tablet contains 2.5 mg zolmitriptan. The other ingredients are mannitol (E421), cellulose microcrystalline, aspartame (E951), croscarmellose sodium, sillica colloidal anhydrous, magnesium stearate (E470b), orange flavor (containing nature-identical flavouring substance(s), flavouring preparation, natural flavouring substance(s), maltodextrin, acacia gum (E414), ascorbic acid (E300), butylated hydroxyanisole (E320)).

What [Invented name] looks like and contents of the pack

[Film-coated tablets only] [Invented name] is a yellow, round shaped, biconvex film coated tablet of 7.5 ± 0.3 mm diameter and with ‘2.5’ debossed on one side and plain on other side. Size of packing: 2 film-coated tablets DE/H/3747/001-002/DC Size of packing: 2, 3 and 6 film-coated tablets

[Orodispersible tablets only] [Invented name] is a white to off-white, round, flat faced beveled edge uncoated tablet of 6.4 ± 0.3 mm diameter and with ‘2.5’ debossed on one side and plain on other side. Size of packing: 2 orodispersible tablets DE/H/3747/001-002/DC Size of packing: 2 and 6 orodispersible tablets

Not all pack sizes may be marketed.

Marketing Authorisation Holder [To be completed nationally]

Manufacturer [To be completed nationally]

This medicinal product is authorised in the Member States of the EEA under the following name

DE/H/3743/001-002/DC

Germany Zolmiless 2,5 mg Filmtabletten Zolmiless 2,5 mg Schmelztabletten Bulgaria Золмитриптан Зентива 2,5 mg филмирани таблетки Золмитриптан Зентива 2,5 mg таблетки, диспергиращи се в устата Lithuania Zolmitriptan Zentiva 2,5 mg plėvele dengtos tabletės Zolmitriptan Zentiva 2,5 mg burnoje disperguojamosios tabletės Romania Zolmitriptan sanofi-aventis 2,5 mg comprimate filmate Zolmitriptan sanofi-aventis 2,5 mg comprimate orodispersabile Sweden Zolmitriptan sanofi-aventis, 2,5 mg filmdragerad tablet Zolmitriptan sanofi-aventis, 2,5 mg munsönderfallande tablett United Kingdom Zolmiless 2.5mg Film coated Tablet Zolmiless 2.5mg Orodispersible Tablet

DE/H/3744/001-002/DC

Germany Zolmibles 2,5 mg Filmtabletten Zolmibles 2,5 mg Schmelztabletten Belgium Zolmitriptan Sanofi Belgium 2,5 mg filmomhulde tabletten Zolmitriptan Sanofi Belgium 2,5 mg orodispergeerbare tabletten Luxembourg Zolmitriptan Sanofi Belgium 2,5 mg comprimés pelliculés Zolmitriptan Sanofi Belgium 2,5 mg comprimés orodispersibles France ZOLMITRIPTAN SANOFI 2,5 mg, comprimé pelliculé ZOLMITRIPTAN SANOFI 2,5 mg, comprimé orodispersible

DE/H/3745/001-002/DC

Germany Zolmilex 2,5 mg Filmtabletten Zolmilex 2,5 mg Schmelztabletten Hungary ALGOMIGRAN 2,5 mg filmtabletta ALGOMIGRAN 2,5 mg szájban diszpergálódó tabletta Poland Zolmitriptan Zentiva, 2,5 mg film-coated tablets Zolmitriptan Zentiva, 2,5 mg orodispersible tablets Slovakia Zolmitriptan Zentiva 2,5 mg filmom obalené tablety Zolmitriptan Zentiva 2,5 mg orodispergovateľné tablety Czech Republic Zolmitriptan Zentiva 2,5 mg potahované tablety Zolmitriptan Zentiva 2,5 mg tablety dispergovatelné v ústech

DE/H/3746/001-002/DC

Germany Zolmisan 2,5 mg Filmtabletten Zolmisan 2,5 mg Schmelztabletten Italy Zolmitriptan Zentiva 2.5 mg compresse Zolmitriptan Zentiva 2,5 mg compresse orodispersibili

DE/H/3747/001-002/DC

Germany Zolmizen 2,5 mg Filmtabletten Zolmizen 2,5 mg Schmelztabletten Austria Zolmitriptan sanofi-aventis 2,5 mg Filmtabletten Zolmitriptan sanofi-aventis 2,5 mg Schmelztabletten Spain Zolmitab 2,5 mg comprimidos recubiertos con película Zolmitab Flas 2,5 mg comprimidos bucodispersables Finland Zolmitriptan sanofi-aventis 2,5 mg kalvopäällysteinen tabletti Zolmitriptan sanofi-aventis 2,5 mg suussa hajoava tabletti Ireland Zolmitriptan Sanofi 2.5mg film-coated tablets Zolmitriptan Sanofi 2.5mg orodispersable tablets Norway Zolmitriptan sanofi-aventis 2,5 mg tabletter Zolmitriptan sanofi-aventis 2,5 mg smeltetabletter Latvia Zolmitriptan Zentiva 2,5 mg apvalkotās tabletes Zolmitriptan Zentiva 2,5 mg mutē disperģējamās tabletes Portugal Zolmitriptano Sanofi¨ Zolmitriptano Sanofi Slovenia Zolmitriptan sanofi-aventis 2,5 mg filmsko obložene tablete Zolmitriptan sanofi-aventis 2,5 mg orodisperzibilne tablete

This leaflet was last revised in {MM/YYYY}.