Zolmitriptan (Page 4 of 7)

8.5 Geriatric Use

Clinical studies of zolmitriptan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) prior to receiving zolmitriptan [see Warnings and Precautions (5.1) ].

The pharmacokinetics of zolmitriptan were similar in geriatric patients (aged > 65 years) compared to younger patients [see Clinical Pharmacology (12.3) ].

8.6 Patients with Hepatic Impairment

After oral zolmitriptan administration, zolmitriptan blood levels were increased in patients with moderate to severe hepatic impairment, and significant elevation in blood pressure was observed in some of these patients [see Warnings and Precautions (5.8) ]. Therefore, adjust the zolmitriptan dose and administer with caution in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.3) and Clinical Pharmacology ( 12) ].


There is no experience with acute overdose of zolmitriptan. Clinical study subjects who received single 50 mg oral doses of zolmitriptan commonly experienced sedation.

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.

The elimination half-life of zolmitriptan is 3 hours [see Clinical Pharmacology (12.1) ]; therefore, monitor patients after overdose with zolmitriptan for at least 15 hours or until symptoms or signs resolve. It is unknown what effect hemodialysis or peritoneal dialysis has on the plasma concentrations of zolmitriptan.


Zolmitriptan tablets, USP contain zolmitriptan, which is a selective 5-hydroxytryptamine1B/1D (5-HT1B/1D ) receptor agonist. Zolmitriptan is chemically designated as (4S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-2-oxazolidinone and has the following chemical structure:

zolmitriptan structual formula

The molecular formula is C16 H21 N3 O2 , representing a molecular weight of 287.36 g/mol. Zolmitriptan is a white to off-white powder that is soluble in methanol and acetone, insoluble in water.

Zolmitriptan tablets, USP are available as 2.5 mg (yellow) and 5 mg (pink) film coated tablets for oral administration. The film-coated tablets contain anhydrous lactose, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, polyethylene glycol 8000, red iron oxide (5 mg tablet), sodium starch glycolate, titanium dioxide and yellow iron oxide (2.5 mg tablet).


12.1 Mechanism of Action

Zolmitriptan binds with high affinity to human recombinant 5-HT1D and 5-HT1B receptors, and moderate affinity for 5-HT1A receptors. The N-desmethyl metabolite also has high affinity for 5-HT1B/1D and moderate affinity for 5-HT1A receptors.

Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of zolmitriptan for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arteriovenous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

12.3 Pharmacokinetics

Absorption, Distribution, Metabolism, and Excretion


Zolmitriptan is well absorbed after oral administration for both zolmitriptan tablets and zolmitriptan orally disintegrating tablets. Zolmitriptan displays linear kinetics over the dose range of 2.5 to 50 mg.

The AUC and Cmax of zolmitriptan are similar following administration of zolmitriptan tablets and zolmitriptan orally disintegrating tablets, but the Tmax is somewhat later with zolmitriptan orally disintegrating tablets, with a median Tmax of 3 hours for zolmitriptan orally disintegrating tablet compared with 1.5 hours for the zolmitriptan tablet. The AUC, Cmax , and Tmax for the active N-desmethyl metabolite are similar for the two formulations.

During a moderate to severe migraine attack, mean AUC0-4 and Cmax for zolmitriptan, dosed as a zolmitriptan tablet, were decreased by 40% and 25%, respectively, and mean Tmax was delayed by one-half hour compared to the same patients during a migraine free period.

Food has no significant effect on the bioavailability of zolmitriptan. No accumulation occurred on multiple dosing.


Mean absolute bioavailability is approximately 40%. The mean apparent volume of distribution is 7 L/kg. Plasma protein binding of zolmitriptan is 25% over the concentration range of 10 to 1000 ng/mL.


Zolmitriptan is converted to an active N-desmethyl metabolite; the metabolite concentrations are about two-thirds that of zolmitriptan. Because the 5HT1B/1D potency of the metabolite is 2 to 6 times that of the parent compound, the metabolite may contribute a substantial portion of the overall effect after zolmitriptan administration.


Total radioactivity recovered in urine and feces was 65% and 30% of the administered dose, respectively. About 8% of the dose was recovered in the urine as unchanged zolmitriptan. Indole acetic acid metabolite accounted for 31% of the dose, followed by N-oxide (7%) and N-desmethyl (4%) metabolites. The indole acetic acid and N-oxide metabolites are inactive.

Mean total plasma clearance is 31.5 mL/min/kg, of which one-sixth is renal clearance. The renal clearance is greater than the glomerular filtration rate suggesting renal tubular secretion.

Specific Populations

Hepatic Impairment

In patients with severe hepatic impairment, the mean Cmax , Tmax , and AUC0-∞ of zolmitriptan were increased 1.5-fold, 2-fold (2 vs. 4 hours), and 3-fold, respectively, compared to subjects with normal hepatic function. Seven out of 27 patients experienced 20 to 80 mm Hg elevations in systolic and/or diastolic blood pressure after a 10 mg zolmitriptan dose. Adjust the zolmitriptan dose in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.3) and Use in Specific Populations (8.6)].

Renal Impairment

Clearance of zolmitriptan was reduced by 25% in patients with severe renal impairment (Clcr ≥ 5 ≤ 25 mL/min) compared to subjects with normal renal function (Clcr ≥ 70 mL/min); no significant change in clearance was observed in patients with moderate renal impairment (Clcr ≥ 26 ≤ 50 mL/min).


Zolmitriptan pharmacokinetics in healthy elderly non-migraineur volunteers (age 65 to 76 years) was similar to those in younger non-migraineur volunteers (age 18 to 39 years).

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