Zomig Nasal spray Flashcards
What is the Therapeutic indication of Zomig nasal spray
Zomig Nasal Spray is indicated for the acute treatment of migraine with or without aura.
What is the Posology of Zomig Nasal Spray
The recommended dose of Zomig Nasal Spray to treat a migraine attack is 5 mg.
Zomig Nasal Spray is administered as a single dose into one nostril. Zomig Nasal Spray provides particularly rapid onset of relief of migraine with the first signs of efficacy apparent within 15 minutes of dosing.
Zomig Nasal Spray provides an alternative non–oral formulation of zolmitriptan to that of Zomig oral tablets and orodispersible tablets. This formulation may also be beneficial where a non–oral route of treatment is either needed or preferred.
If symptoms persist or return within 24 hours a second dose has been shown to be effective. If a second dose is required, it should not be taken within 2 hours of the initial dose.
Zomig Nasal Spray is effective whenever the nasal spray is administered during a migraine attack; although it is advisable that Zomig Nasal Spray is 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 Zomig Nasal Spray in a 24 hour period should not exceed 10 mg.
Zomig Nasal Spray is not indicated for prophylaxis of migraine.
What are the contraindications of Zomig nasal spray?
Zomig Nasal Spray is contraindicated in patients with:
* Hypersensitivity to the active substance or to any of the excipients
* Uncontrolled hypertension
* Ischaemic heart disease
* Coronary vasospasm/Prinzmetal’s angina
* A history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA)
* Concomitant administration of Zomig Nasal Spray with ergotamine or ergotamine derivatives or other 5-HT1 receptor agonists.
What are the pharmacodynamic properties of Zomig Nasal Spray?
Pharmacotherapeutic group: Selective serotonin (5HT1) agonists. ATC code: N02CC03
What is the mechanism of action of Zomig Nasal Spray?
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 5HT1B/1D receptor is predominantly 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.
What are the pharmacokinetic properties of zomig nasal spray?
Zolmitriptan, following intranasal administration, is rapidly absorbed with detectable levels in the plasma within 5 minutes of dosing. A proportion of the dose seems to be directly absorbed in the naso-pharynx. On average 40% of Cmax of the parent compound, zolmitriptan, is achieved within 15 minutes. The appearance in plasma of the active metabolite, N-desmethylzolmitriptan, which is partly formed through first-pass metabolism, is delayed by 15 to 60 minutes post-dose. Cmax of the parent compound, zolmitriptan is achieved after 3 hours. Plasma concentrations are sustained for up to 4 to 6 hours. Elimination of zolmitriptan and the active metabolite N-desmethylzolmitriptan after oral and intranasal delivery appear similar; the mean elimination half-life (t½) for both zolmitriptan and N-desmethylzolmitriptan are approximately 3 hours. The bioavailability of intranasal relative to oral administration is 102%. In healthy volunteers after single and multiple intranasal doses, zolmitriptan and its active metabolite N-desmethylzolmitriptan display dose proportional AUC and Cmax over the range 1 to 5 mg. There is no evidence of accumulation of zolmitriptan after multiple intranasal dosing.
The plasma concentrations and elimination pharmacokinetics of zolmitriptan and the three major metabolites for the nasal spray and conventional tablet formulations are similar.
Absorption is rapid with 75% of Cmax achieved within 1 hour and plasma concentrations are sustained subsequently for 4 to 6 hours. After oral administration zolmitriptan absorption is unaffected by the presence of food.
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-desmethyl metabolite ) is an active metabolite which is also a 5H 1B/1D agonist and is 2 to 6 times as potent, in animal models, as zolmitriptan. Metabolism of zolmitriptan is dependent on CYP1A2 and the metabolism of the active metabolite N-desmethylzolmitriptan is via the monoamine oxidase A (MAOA) enzyme system. Plasma concentrations of N-desmethyzolmitriptan are approximately half those of the parent drug, hence it would therefore be expected to contribute to the therapeutic action of Zomig. 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 plasma half-life (T½) of zolmitriptan was 4.7 hours in healthy volunteers, 7.3 hours in patients with moderate liver disease and 12 hours in those with severe liver disease. The corresponding T½ values for the N-desmethylzolmitriptan metabolite were 5.7 hours, 7.5 hours and 7.8 hours respectively.
No studies have been undertaken to characterise the pharmacokinetics of intranasally administered zolmitriptan in patients with hepatic impairment.
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. These findings originate from studies with zolmitriptan tablets.
