Zolmitriptan was introduced in 1990 and subsequently approved for medical use in November 1997 by the U.S. Food and Drug Administration (FDA). Zolmitriptan belongs to a class of drugs called triptans, which act as selective serotonin receptor agonists, targeting specific serotonin receptors (primarily 5-HT1B and 5-HT1D) in the brain. Triptans are a type of pharmaceutical medication work by targeting serotonin receptors in the brain to reduce inflammation and constrict blood vessels, thereby stopping a migraine attack.
BRAND NAMES
Zomig- As the brand name for zolmitriptan, Zomig is a triptan drug that acts as a selective serotonin receptor agonist to treat acute migraine attacks. It is not used to prevent future migraines as it happens, with the goal of stopping or reversing the symptoms.
It is taken by mouth and swallow it with the water or crumbling tablet or as a nasal spray.
MECHANISM OF ACTION
As a triptan, zolmitriptan functions as a selective serotonin receptor agonist, mainly targeting the 5-HTand 5-HT subtypes. Its mechanism of action involves both peripheral and central effects that treat acute migraine attacks. This action causes blood vessels to constrict (vasoconstriction) and also inhibits the release of inflammatory neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P, from trigeminal nerves. These combined effects reduce the pain, nausea, and other symptoms of a migraine attack.
PHARMACOKINETICS
Absorption
Zolmitriptan is absorbed rapidly, with the speed depending on the formulation. The oral bioavailability is approximately 40% due to first-pass metabolism in the liver, while the nasal spray formulation offers faster absorption and onset of action.
Zolmitriptan from a nasal spray enters the bloodstream very quickly, often within 2–5 minutes. This speed is significantly faster than the 10–15 minutes it takes for the oral tablet form.
Distribution
Zolmitriptan exhibits a volume of distribution ranging from 7 to 8.4 L/kg.
Metabolism
Zolmitriptan metabolism results in three major metabolites: an active N-desmethyl metabolite, as well as inactive N-oxide and indole acetic acid metabolites. Zolmitriptan is predominantly metabolized in the liver, primarily by the cytochrome P450 (CYP) enzyme system. This process generates an active metabolite, N-desmethyl-zolmitriptan, along with other inactive metabolites.
Excretion
Zolmitriptan is primarily cleared through liver metabolism and subsequently excreted in urine (65%) and feces (35%). The total process has an elimination half-life of approximately three hours.
PHARMACODYNAMICS
Zolmitriptan is a triptan drug primarily used to treat acute migraine and cluster headaches. Its pharmacodynamics, or effects on the body, are based on its action as a selective agonist for specific serotonin receptors. Triptans, including zolmitriptan, are thought to affect the trigeminovascular system through both peripheral and central nervous system pathways.
Administration
The device is a single-use item and must be discarded after administering one dose to prevent cross-contamination. This prevents contamination and helps ensure the full, correct dose is given. Following administration, the patient should breathe gently through the mouth for a short duration. Experiencing liquid in the nose or throat is normal. Taking it with food or on an empty stomach does not affect how the medicine works. ODTs melt in your mouth and don't require water to swallow. Do not break or cut the ODT.
Dosage and strengths
Oral- The strength of the Zolmitriptan oral tablets are 2.5 mg (scored) and 5 mg.
For the 1.25 mg dose, a 2.5 mg scored tablet can be split.
Orally disintegrating tablets-The strength of the Zolmitriptan Orally disintegrating tablets are 2.5 mg and 5 mg.
ODT's disintegrate quickly when placed on the tongue, and splitting them can disrupt their intended effect.
Nasal spray-The strength of the Zolmitriptan nasal spray is 2.5 mg and 5 mg.
In adults and children 12 and older, the spray is typically administered into one nostril.
Drug interactions
Zolmitriptan has several drug interactions, ranging from severe to minor. Combining this with other medications that increase serotonin levels may cause serotonin toxicity, which can be life-threatening. Zolmitriptan should not be taken within 24 hours of other triptans or ergotamine-containing medications due to the risk of additive vasospastic effects. It should also be avoided within two weeks of taking a monoamine oxidase (MAO) inhibitor.
Food interactions
Avoid or limit alcohol consumption while taking Zolmitriptan. High doses of caffeine can decrease the metabolism of zolmitriptan, which increases the risk of side effects, such as increased nervousness and blood pressure. However, low-to-moderate caffeine use is generally safe. Since certain foods and drinks can trigger migraines, you may want to avoid them to prevent additional headaches.
Contraindications
Zolmitriptan is contraindicated in patients with a history of cardiovascular disease, as it can cause significant and potentially serious vasoconstriction. This includes individuals with ischemic heart disease, such as angina pectoris or a history of myocardial infarction, as well as those with coronary artery vasospasm (Prinzmetal's angina), uncontrolled hypertension, peripheral vascular disease, or ischemic bowel disease.
Side effects
- feeling warm or cold.
- drowsiness, dizziness or faintness.
- dry mouth.
- nausea.
- heartburn.
- sweating.
- Tingling or numbness.
- Pressure or tightness.
- Weakness or fatigue.
Overdose
- Severe drowsiness or faintness.
- Chest pain, pressure, or heaviness.
- Rapid or irregular heartbeat.
- Shortness of breath or trouble breathing.
- Vomiting.
- Numbness or tingling.
- Severe abdominal pain, especially with bloody diarrhea.
- Increased blood pressure.
Toxicity
Common signs of toxicity included tachycardia, difficulty breathing, and vomiting. In adults, zolmitriptan overdose has been associated with high blood pressure, increased heart rate, and drowsiness. In addition, zolmitriptan use has been associated with two reported cases of liver toxicity. While there is a potential risk of medication overuse headaches, this can be reduced through proper patient education on correct medication usage. In instances of severe drug overdose, it is advised to secure and maintain a clear airway, support adequate breathing, and preserve circulatory function.
Storage
Oral tablets- Store at a controlled room temperature, generally between 20°C and 25°C. Keep the tablets in a tightly closed, light-resistant container to protect them from light and moisture.
Orally disintegrating tablets- Do not remove the ODT from its blister pack until you are ready to take it. The blister pack protects the delicate tablet from moisture. If your ODTs come in a foil pouch, keep the blister pack inside the pouch until you are ready to use the medicine.
Nasal spray- Store at room temperature (20°C to 25°C) and protect from light and moisture. Never freeze the nasal spray.
