Zolmitriptan

For patients taking MAO-A inhibitors, a maximum dose of 5 mg in 24 hours is recommended.

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.

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

For patients with severe hepatic impairment, a maximum dose of 5 mg in 24 hours is recommended.

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.

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 zolmitriptan and an SSRI or SNRI is necessary, particularly during treatment initiation and dosage increases.

A maximum dose of 5 mg zolmitriptan in 24 hours is recommended in patients taking cimetidine.

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. 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 (eg ciprofloxacin).

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.

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 20mg 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.

Oral administration

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.

Nasal administration

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: