ZOMIG Film-coated tablet Ref.[50369] Active ingredients: Zolmitriptan

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 no 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. Stroke and other cerebrovascular events have been reported in patients treated with 5HT_1B/1D agonists. It should be noted that migraineurs may be at risk of certain cerebrovascular events.

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 5HT_1B/1D agonists, coronary vasospasm, angina pectoris and myocardial infarction have been reported. ‘Zomig’ 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 5HT_1B/1D receptor 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 5HT_1B/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.

Serotonin syndrome has been reported with combined use of triptans and serotonergic drugs, such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). Serotonin Syndrome is a potentially life-threatening condition and 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 if concomitant treatment with ZOMIG and an SSRI or SNRI is necessary, particularly during treatment initiation and dosage increases (see Section 4.5).

Withdrawal of the serotonergic drugs usually brings about a rapid improvement. Treatment depends on the type and severity of the symptoms.

Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) has been reported following concomitant treatment with triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). These reactions can be severe. If concomitant treatment with zolmitriptan and an SSRI or SNRI is clinically warranted, appropriate observation of the patient is advised, particularly during treatment initiation, with dose increases, or with addition of another serotonergic medication (see section 4.5).

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.

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

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.

Data from healthy subjects suggests 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 (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 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 (N-desmethylzolmitriptan) 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 specific inhibitors of CYP 1A2 cannot be excluded. Therefore, the same dosage reduction is recommended with compounds of this type, such as fluvoxamine and the quinolones (eg ciprofloxacin).

Selegiline (a MAO-B inhibitor) and fluoxetine (an SSRI) did not result in any pharmacokinetic interaction with zolmitriptan. However, there have been 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 5HT_1B/1D receptor agonists, zolmitriptan could delay the absorption of other medicinal products.

Concomitant administration of other 5HT_1B/1D agonists within 24 hours of zolmitriptan treatment should be avoided. Similarly, administration of zolmitriptan within 24 hours of the use of other 5HT_1B/1D agonists should be avoided.

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

Pregnancy

The safety of this medical product for use in human pregnancy has not been established. Evaluation of experimental animals 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.

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

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 definitions apply to the incidence of the undesirable effects: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

The following undesirable effects have been reported following administration of zolmitriptan:

Certain symptoms may be part of the migraine attack itself.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Tel: +357 22608607, Fax: +357 22608669, website: www.moh.gov.cy/phs.

Not applicable.