ZOMIG Nasal spray Ref.[8083] Active ingredients: Zolmitriptan

Zomig Nasal Spray should only be used where 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 Zomig Nasal Spray in hemiplegic or basilar migraine. Migraineurs may be at risk of certain cerebrovascular events. Cerebral haemorrhage, subarachnoid haemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with 5HT_1B/1D agonists.

Zomig Nasal Spray 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. In patients with risk factors for ischaemic heart disease, cardiovascular evaluation prior to commencement of treatment with this class of compounds, including Zomig Nasal Spray, is recommended (see Section 4.3). 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 agonists, atypical sensations over the precordium (see Section 4.8) have been reported after the administration of Zomig Nasal Spray.

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.

As with other 5HT_1B/1D agonists, there have been rare reports of anaphylaxis/anaphylactoid reactions in patients receiving Zomig Nasal Spray.

Excessive use of an acute anti-migraine medicinal product may lead to an increased frequency of headache, potentially requiring withdrawal of treatment.

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 Zomig Nasal Spray and an SSRI or SNRI is clinically warranted, particularly during treatment initiation and dosage increases (see section 4.5).

From studies using oral zolmitriptan tablets, there is no evidence that concomitant use of migraine prophylactic medications has any effect on the efficacy or unwanted effects of Zomig Nasal Spray (for example beta-blockers, oral dihydroergotamine, pizotifen).

The pharmacokinetics and tolerability of Zomig oral tablets were unaffected by acute symptomatic treatments such as paracetamol, metoclopramide and ergotamine.

Concomitant administration of other 5HT_1B/1D agonists within 24 hours of Zomig Nasal Spray treatment should be avoided.

Data from healthy subjects suggest that there are no pharmacokinetic or clinically significant interactions between Zomig Nasal Spray and ergotamine, however, the increased risk of coronary vasospasm is a theoretical possibility. Therefore, it is advised to wait at least 24 hours following the use of ergotamine containing preparations before administering Zomig Nasal Spray. Conversely it is advised to wait at least six hours following use of Zomig Nasal Spray before administering any ergotamine preparation (see Section 4.3).

Following co-administration of moclobemide, a specific MAO-A inhibitor, and Zomig oral tablets, 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 Zomig Nasal Spray in 24 hours is recommended in patients taking an MAO-A inhibitor.

Following the co-administration of cimetidine, a general P450 inhibitor, and Zomig oral tablets, 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 Zomig Nasal Spray 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).

Fluoxetine did not affect the pharmacokinetic parameters of zolmitriptan in a study using oral zolmitriptan tablets. 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).

As with other 5HT_1b/1d 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.

The absorption and pharmacokinetics of Zomig is unaltered by prior administration of the sympathomimetic vasoconstrictor, xylometazoline.

Pregnancy

Zomig Nasal Spray should be used in pregnancy only if the benefits to the mother justify potential risk to the foetus. There are no studies in pregnant women, but there is no evidence of teratogenicity in animal studies (see Section 5.3).

Breast-feeding

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 Zomig Nasal Spray to women who are breast-feeding.

There was no significant impairment of performance of psychomotor tests with doses up to 20 mg oral Zomig. Zomig Nasal Spray has no or negligible influence on the ability to drive and use machines. However it should be taken into account that somnolence may occur.

Summary of the safety profile

Zomig is well tolerated. Adverse reactions are typically mild/moderate, transient, not serious and resolve spontaneously without additional treatment.

Possible adverse reactions tend to occur within 4 hours of dosing and are no more frequent following repeated dosing.

Tabulated list of adverse reactions

Adverse reactions are classified according to frequency and system organ class. Frequency categories are defined according to the following convention: 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). The following undesirable effects have been reported following administration with zolmitriptan:

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 Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.

Not applicable.