Zolmitriptan 5 mg Film-coated Tablets

Summary of Product Characteristics Updated 16-Jul-2025 | Glenmark Pharmaceuticals Europe Ltd

1. Name of the medicinal product

Zolmitriptan 5 mg Film-coated Tablets

2. Qualitative and quantitative composition

5 mg

Each film-coated tablet contains 5.0 mg zolmitriptan

Excipient: Lactose, anhydrous 205.00 mg per tablet

For a full list of excipients, see section 6.1.

3. Pharmaceutical form

Film-coated tablet

5 mg

Pink coloured, round, biconvex film-coated tablets debossed with 498 on one side and plain on other side (diameter approximately: 8.5 mm).

4. Clinical particulars
4.1 Therapeutic indications

Zolmitriptan is indicated for the acute treatment of migraine headache with or without aura. It is not indicated for prophylaxis.

4.2 Posology and method of administration

The recommended dose of zolmitriptan to treat a migraine attack is 2.5 mg.

If symptoms return 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 doses, subsequent attacks can be treated with 5 mg doses of zolmitriptan. Caution is advised due to an increased incidence of undesirable effects. A controlled clinical study failed to demonstrate superiority of the 5 mg dose over the 2.5 mg dose. Nevertheless a 5 mg dose may be of benefit for some patients.

Zolmitriptan is equally effective whenever the tablets are taken during a migraine attack; although it is advisable that zolmitripan 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. Not more than 2 doses of Zolmitriptan Film-coated Tablets should be taken in any 24 hour period.

Use in patients aged over 65 years

Zolmitriptan is not recommended for elderly adults over 65 years due to a lack of data on safety and efficacy (see section 5.1 5.2).

Patients with hepatic impairment

Patients with mild or moderate hepatic impairment require no dose adjustment, however for patients with severe hepatic impairment, a maximum dose of 5 mg in 24 hours is recommended.

Patients with renal impairment

No dosage adjustment required in patients with a creatinine clearance of more than 15 ml/min. (see Section 5.2)

Interactions requiring dose adjustment (see section 4.5)

For patients taking MAO-A inhibitors, specific inhibitors of CYP1A2 such as fluvoxamine and the quinolones (eg ciprofloxacin), or for patients taking cimetidine, a maximum dose of 5 mg zolmitriptan in 24 hours is recommended.

Use in Children below age 12 years

Zolmitriptan is not recommended for use in children below age 12 due to a lack of data on safety and efficacy (see sections 5.1 and 5.2).

Adolescents age 12 - 17 years

The efficacy of zolmitriptan was not demonstrated in a placebo controlled clinical trial for patients aged 12 to 17 years. Therefore the use of zolmitriptan in adolescents age 12 to 17 years is not recommended.

Method of administration:

The film-coated tablet should be swallowed with a drink of water.

4.3 Contraindications

• Hypersensitivity to the active substance zolmitriptan or to any of the excipients

• Moderate to severe hypertension, and mild uncontrolled hypertension

• A history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA)

This class of compounds (5-HT1B/1D receptor agonists), has been associated with coronary vasospasm, as a result, patients with ischaemic heart disease were excluded from clinical trials. Therefore Zolmitriptan Film-coated Tablets should not be given to patients who have had myocardial infarction or have ischaemic heart disease, coronary vasospasm (Prinzmetal's angina), peripheral vascular disease or patients who have symptoms or signs consistent with ischaemic heart disease.

Concurrent administration of ergotamine, ergotamine derivatives (including methysergide), sumatriptan, naratriptan and other 5-HT1B/1D receptor agonists with zolmitriptan is contraindicated (see section 4.5).

Zolmitriptan is contraindicated in patients with a creatinine clearance of less than 15 ml/min.

4.4 Special warnings and precautions for use

Zolmitriptan 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. Zolmitriptan is not indicated for use in hemiplegic, basilar or ophthalmoplegic 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, coronary vasopasm, angina pectoris and myocardial infarction have been reported. Zolmitriptan Film-coated Tablets 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.

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.

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.

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 triptans, and Selective Serotonin 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) (see Section 4.4).

This medicinal product contains lactose. Patients with rare hereditary problems of galacotose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies were performed with caffeine, ergotamine, dihydroergotamine, paracetamol, metoclopramide, pizotifen, fluoxetine, rifampicin and propranolol and no clinically relevant differences in the pharmacokinetics of zolmitriptan or its active metabolite were observed.

The pharmacokinetics and tolerability of zolmitriptan were unaffected by acute symptomatic treatments such as paracetamol, metoclopramide and ergotamine. Concomitant administration of other 5HT1B/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.

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 preparation (see Section 4.3).

Following administration of moclobemide, 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 an 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 (eg, ciprofloxacin).

Selegiline (a MAO-B inhibitor) and fluoxetine does not affect the pharmacokinetic parameters of zolmitriptan. Therapeutic doses of the specific serotonin reuptake inhibitors, fluoxetine, sertraline, paroxetine and citalopram do not inhibit CYP1A2. However, Serotonin Syndrome has been reported during combined use of triptans, and SSRIs (e.g. fluoxetine, paroxetine, sertraline) and SNRIs (e.g. venlafaxine, duloxetine) (See section 4.4).

Zolmitriptan could delay the absorption of other medicinal products.

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 zolmitriptan to women who are breast-feeding. Infant exposure should be minimised by avoiding breast feeding for 24 hours after treatment.

4.7 Effects on ability to drive and use machines

There was no significant impairment of performance of psychomotor tests with doses up to 20 mg of zolmitriptan in a small group of healthy individuals. Caution is recommended in patients performing skilled tasks (eg driving or operating machinery) as drowsiness and other symptoms may occur during a migraine attack.

4.8 Undesirable effects

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

The following table lists the adverse reactions associated with zolmitriptan therapy.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows:

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).

System organ class

Frequency

Common

Uncommon

Rare

Very rare

Immune System Disorders

Hypersensitivity reactions including urticaria, angioedema and anaphylactic reactions

Nervous System Disorders

Abnormalities or disturbances of sensation

Dizziness

Headache

Hyperaesthesia

Paraesthesia

Somnolence

Warm sensation

Cardiac Disorders

Palpitations

Tachycardia

Angina pectoris

Coronary Vasospasm

Myocardial Infarction

Vascular Disorders

Transient increases in systemic blood pressure

Gastrointestinal Disorders

Abdominal Pain

Dry mouth

Nausea

Vomiting

Bloody diarrhoea

Gastrointestinal infarction or necrosis

Gastrointestinal ischaemic events

Ischaemic colitis

Splenic Infarction

Muscosceletal and Connective Tissue Disorders

Muscle weakness

Myalgia

Renal and Urinary Disorders

Polyuria

Increased urinary frequency

Urinary Urgency

General Disorders and Administration Site Conditions

Asthenia

Heaviness, tightness, pain or pressure in throat, neck limbs or chest

Certain symptoms may be part of the migraine attack itself.

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) 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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics; antimigraine preparations; Selective serotonin (5HT1) agonists.

ATC code: N02CC03

In pre-clinical studies, zolmitriptan has been demonstrated to be a selective agonist for the vascular human recombinant 5HT1B and 5HT1D receptor subtypes. Zolmitriptan is a high affinity 5HT1B/1D receptor agonist with modest affinity for 5HT1A receptors. Zolmitriptan has no significant affinity (as measured by radioligand binding assays) or pharmacological activity at 5HT2-, 5HT3-, 5HT4-, alpha1-, alpha2-, or beta1-, adrenergic; H1-, H2-, histaminic; muscarinic; dopaminergic1, or dopaminergic2 receptors. The 5HT1D receptor is predominately located presynaptically at both the peripheral and central synapses of the trigeminal nerve and preclinical studies have shown that zolmitriptan is able to act at both these sites.

In clinical studies 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 is consistently effective in migraine with or without aura and in menstrually associated migraine. Zolmitriptan, if taken during the aura, has not been demonstrated to prevent migraine headache and therefore Zolmitriptan Film-coated Tablets 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

Zolmitriptan is rapidly and well absorbed (at least 64%) after oral administration to man. The mean absolute bioavailability of the parent compound is approximately 40%. There is an active metabolite (183C91, the N-desmethyl metabolite) which is also a 5HT1B/1D 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 183C91, display dose-proportional AUC and Cmax over the dose range 2.5 to 50 mg. Absorption is rapid with 75% of Cmax achieved within 1 hour and plasma concentrations are sustained subsequently for 4 to 6 hours. 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 a reduced rate of gastric emptying observed during a migraine attack.

Zolmitriptan is eliminated largely by hepatic biotransformation followed by urinary excretion 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 (183C91) is active whilst the others are not. Plasma concentrations of 183C91 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.

The metabolism of zolmitriptan is reduced in hepatic impairment in proportion to the extent of the impairment. Zolmitriptan AUC and Cmax were increased by 226% and 50%, respectively and the half life was prolonged to 12 h in subjects with severe liver disease compared to healthy subjects. Exposure to the metabolites, including the active metabolite was reduced.

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 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 were similar to those in healthy young volunteers.

5.3 Preclinical safety data

In preclinical acute and chronic toxicity studies, toxic effects were only observed at dosages considerably above the maximum therapeutic dose in humans.

Results from in vitro and in vivo genotoxicity studies show that, under the conditions of clinical use, no genotoxic effects of zolmitriptan are anticipated.

In long-term studies to investigate the tumorigenic potential in mice and rats, no tumours relevant to clinical use were found.

As with other 5HT1B/1D receptor agonists, zolmitriptan is also bound to melanin.

6. Pharmaceutical particulars
6.1 List of excipients

5 mg

Tablet core

Lactose anhydrous

Cellulose microcrystalline

Sodium Starch Glycolate type A

Magnesium Stearate

Tablet Coat

Hypromellose

Titanium dioxide (E 171)

Macrogol 400

Macrogol 8000

Iron Oxide Red (E 172)

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Cold form aluminium foil blisters with plain aluminium foil lidding in cartons containing 3, 6 or 12 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Glenmark Pharmaceuticals Europe Limited

Laxmi House, 2-B Draycott Avenue,

Kenton, Harrow, Middlesex, HA3 0BU,

United Kingdom

8. Marketing authorisation number(s)

PL 25258/0083

9. Date of first authorisation/renewal of the authorisation

08/07/2025

10. Date of revision of the text

08/07/2025

Company Contact Details
Glenmark Pharmaceuticals Europe Ltd
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+44 (0)1923 251137

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www.glenmarkpharma.com

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0800 458 0383

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