Overview:
Zolmitriptan is used as a medication to relieve the symptoms of migraine headaches. Sometimes these headaches occur along with sensitivity to sound and light. Selective serotonin receptor agonists are the class of which Zolmitriptan is a part. It constricts the blood vessels present around the brain, which helps stop the signals of pain from getting transferred to the brain. It also prohibits the release of a few natural factors, which are the causative agents behind certain symptoms such as nausea, pain, etc. Zolmitriptan does not cure migraine headaches but is used to manage their symptoms.
How Does the Zolmitriptan Work?
Zolmitriptan belongs to the group of triptans, also known as selective serotonin receptor agonists. It targets, especially the 5-HT 1B/1D serotonin receptors. Zolmitriptan forms a bond with these receptors in neurons and also in the blood vessels of the brain. Many studies have mentioned that this bond formed by Zolmitriptan helps in the constriction of the blood vessels and blocks the chemicals which are responsible for the increase in inflammation.
It also pacifies the factors that trigger the headache and contribute to migraine headaches. It does not cure or prevent migraines but can be used for their management. It works for both types of migraines, such as with aura or without aura.
How Is Zolmitriptan Used?
Zolmitriptan can be seen in tablet form and in a tablet that disintegrates being taken orally. It is taken as soon as the first sign of a migraine headache is noticed. Sometimes the symptoms of migraine headache improve after taking Zolmitriptan, and then the symptoms recur after about two or more hours, in such cases, it is indicated to take another tablet of Zolmitriptan. But, if the symptoms do not pacify after taking Zolmitriptan, it is not advised to take another tablet of the drug without notifying the physician. The physician will prescribe a proper dosage of the tablets that can be taken within 24 hours. The Zolmitriptan tablet should be taken as advised by the physician, and the dose taken should be followed exactly as advised or prescribed by the physician. As these tablets are oral disintegrating tablets, they dissolve as soon as placed on the tongue and can be swallowed with the help of saliva. If the patient takes more tablets of Zolmitriptan than are recommended or prescribed, the migraine headaches can become worse than before. Patients should avoid taking more than two tablets in 24 hours.
What Are the Prescribed Doses and Forms of Zolmitriptan?
The dose of the Zolmitriptan medication varies from patient to patient. The physician will set the dose after examining the patient properly. It is not advised to adjust the dose without the physician’s consent. The dose consumed by the patient depends upon the strength of the medicine. The disease or medical condition decides the number of doses to be taken each day, the time difference between 2 doses, and how long the medication should be taken. The details of the dosage are mentioned as follows:
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Oral Tablets: In adults, 1.25 or 2.5 milligrams (mg) of the tablet can be taken as a single dose. If the symptoms recur after two or more hours, then the dose can be repeated. It is prohibited to take more than 5 mg of Zolmitriptan in a single dose or more than 10 mg in a period of 24 hours. In children, it is not recommended to use this medicine.
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Oral Disintegrating Tablets: In adults, 2.5 mg of Zolmitriptan is placed on the surface of the tongue. If the migraine headache recurs after two or more hours from the administration of the first dose, then the same dose can be repeated. The medication should not be taken for more than 5 mg in a single dose or 10 mg or more in 24 hours. For children, the use of this medicine is not advised.
Directions:
The patient may split the tablet of Zolmitriptan in half if the dose prescribed is lower than 2.5 mg but the oral disintegrating tablets should not be broken or split. It is advised that the hands should be dry while taking the medicine out of its foil pack. The tablet should be placed on the tongue as soon as it is taken out of the package. The tablet will dissolve and be swallowed by saliva. Water is not needed to swallow this tablet, as it readily dissolves with the help of saliva. Whenever the patient is ready to take the medicine, the tablet should be taken out of its packaging.
Warnings:
The medicine should be kept out of reach of children, and it should also be kept away from pets. It should be stored at room temperature away from moisture, light, and heat. The orally disintegrating tablets should be disposed of if not taken immediately after taking them out from the packaging. The FDA’s (Food and Drug Administration) official website for safe disposal of medications should be visited before disposing of the medicines. Do not take Zolmitriptan more than advised, as it may make the situation worse.
For Patients:
What Is Migraine Headache?
A headache is defined as a simple but continuous pain in the head. A migraine headache is elaborated as a recurrent, throbbing headache that is often unilaterally present, and conditions like nausea, disturbed vision, etc accompany it. Migraine headaches are a problem that is widespread and can be seen in various regions of the world. Other symptoms like vomiting, dizziness, increased sensitivity to sound or light, extreme reaction to touch or being unable to bear a particular smell, tingling sensation, or numbness around the face or in the extremities can be seen in patients with migraine headaches. Migraine headaches are divided into 2 types such as migraine with aura and migraine without aura. An aura is a sensory disturbance that is temporarily occurring before the headache or during the headache. A few examples of common auras are visual disturbances, phantosmia (the presence of a phantom smell that is not present in reality), and a disorganized or confused way of thinking.
Why Should Zolmitriptan Be Taken?
Zolmitriptan is prescribed to pacify the symptoms of migraine headaches. The symptoms generally include severe throbbing pain in the head, nausea, vomiting, and increased sensitivity to light and sound. When the first signs or symptoms of migraine headache occur, Zolmitriptan should be taken. It does not cure or prevent migraines, but it helps in the management of the symptoms. Zolmitriptan should be taken as advised by the physician to relieve the symptoms.
How Effective Is Zolmitriptan?
Zolmitriptan comes from the triptan family of drugs. It is available as an oral tablet, an oral disintegrating tablet, and a nasal spray. It is used to manage the symptoms of migraines, not treat them. A single oral dose was effective in many cases and was observed to relieve the symptoms of the migraine headache. In a few cases, it was observed that the severe or moderate pain was relieved by Zolmitriptan within two hours of taking it. In some cases, a slight change in the result was observed, the result was a little better where higher doses of 5 mg or 20 mg oral tablets were given to the patients. However, in the cases with a 10 mg dosage, more adverse events were seen. These adverse events were reported for a short duration, and the intensity of severity recorded was mild or moderate. The results in the case of patients who were given 5 mg Zolmitriptan through nasal spray were similar to those for the tablets taken orally, or can also be called better if the effectiveness in a short time is taken into consideration.
Know More About the Zolmitriptan in the Following Points:
Points to Remember Before Taking Zolmitriptan:
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The physician or pharmacist should be notified about any drug allergy the patient has.
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The Zolmitriptan medication should be avoided if the patient has taken any of the medicines in the past 24 hours such as another type of selective serotonin receptor agonist such as Almotriptan, Eletriptan, Naratriptan, Frovatriptan, etc, or any type of ergot medications like Bromocriptine, Ergonovine, Methysergide, etc.
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The physician should be notified about the other medications, vitamin supplements, other nutritional supplements, or herbal products the patient plans to take. Also, the use of Acetaminophen, antidepressants, nonsteroidal anti-inflammatory drugs, oral contraceptives, selective serotonin reuptake inhibitors, and a few other categories of drugs should be informed to the physician.
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Any history of cardiovascular diseases such as angina pectoris, myocardial infarction, etc should be told to the physician before starting the Zolmitriptan.
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The physician should be informed about the current pregnancy or if the patient is planning to become pregnant.
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There are a few other conditions or syndromes such as Raynaud’s disease or ischaemic bowel diseases where the use of Zolmitriptan is contraindicated.
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No specific diet needs to be followed while taking Zolmitriptan unless instructed by the physician.
What Are the Side Effects of Taking Zolmitriptan?
If the following symptoms persist, then the physician should be informed:
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Drowsiness.
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Dry mouth.
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Sweating.
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Heartburn.
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Dizziness
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Fainting
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Feeling cold or warm etc.
There are a few severe symptoms that may occur and where emergency help should be sought mentioned as follows:
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Heaviness, pain, and tightness in the chest, neck, and jaw area.
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Slow or difficulty in speaking.
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Weakness or numbness in the extremities.
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Irregular and fast heartbeats.
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Bloody diarrhea.
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Sudden, impromptu, and severe abdominal pain.
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Bluish discoloration of the fingers and toes.
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Paleness of the skin.
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Swollen lips, tongue, face, or eyes.
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Difficulty breathing.
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Difficulty swallowing.
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Rashes or hives.
How to Store or Dispose of Zolmitriptan?
The container of the medication should not be changed, and the medicine should be kept in the same container it came in. The cap or lid of the container should be tightly closed. The medication should be kept away from children. It should be stored at room temperature, away from light, and away from raised temperatures or heat. Also, the surroundings should be moisture free.
The patient should dispose of the tablet if it was not taken immediately after taking it out of the packaging. There are certain ways to dispose of the medicines so that they do not come into contact with children, pets, or other people who are contraindicated from taking the medicine. These certain ways of disposal of medicines are explained in the Food and Drug Administration’s (FDA) safe disposal of medicines website. Preventive measures should be taken to prevent young children from opening medicine containers. It should be stored somewhere away and out of sight and reach of the children.
What Should Be Done in the Case of Zolmitriptan Overdose?
Emergency help should be sought as soon as the symptoms occur. If the patient has seizures, faints, or collapses, then the patient should be taken to the emergency room as soon as possible. One moderate example of Zolmitriptan overdose is extreme drowsiness; if extreme drowsiness occurs in the patient, then the physician should be notified about it.
What Should Be Done If a Dose Is Missed?
If the prescribed dose is missed due to some reason, then the dose should be taken as soon as the patient can, but if it is the time of the second dose, then the previous missed dose should be skipped. One should restart following the prescribed timing of the doses. Taking double doses of the medication should be avoided, as it may lead to adverse events.
What Else Should Be Known About Taking Zolmitriptan?
The patient's records of the incidence of migraine headaches should be kept. The dosage should not be adjusted without the advice of the physician. Self-medication should be prohibited. Persistent intake of the medication without the physician’s consent may worsen the situation. Sharing your prescription or medicines should be avoided, as the dosage varies from patient to patient. The medication should be stopped by following the instructions of the physician to prevent withdrawal symptoms.
For Doctors:
What Are the Pharmacological Aspects of Zolmitriptan?
It is a novel 5-hydroxytryptamine (5HT)1B/1D receptor agonist along with proven efficacy in the acute treatment of migraine either with aura or without aura. It showed robust oral pharmacokinetics and was also able to inhibit trigeminovascular activity centrally and also peripherally in preclinical studies.
Mechanism of Action:
Zolmitriptan makes bonds with human recombinant 5-HT1D and 5-HT1B as Zolmitriptan shows high affinity towards them and moderate affinity towards 5-HT1A receptors. Similarly, N-desmethyl metabolite shows a high affinity for 5-HT1B/1D but shows a moderate affinity for 5-HT1A receptors. Migraine headaches occur mostly due to the local cranial vasodilation and can be through the release of some sensory neuropeptides through the nerve endings of the trigeminal system, sensory neuropeptides such as a vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide are released. The therapeutic activity of Zolmitriptan for the treatment of migraine headache symptoms is considered to be due to its agonist action at the 5HT1B/1D receptors present in the intracranial blood vessels and sensory nerves in the trigeminal system. This activity results in cranial vessel constriction and inhibits pro-inflammatory neuropeptide release. It also crosses the blood-brain barrier proved by the presence of radioactive 3H- Zolmitriptan labels within the cells of trigeminal nucleus caudalis and nucleus tractus solitarius.
Pharmacodynamics:
Zolmitriptan is primarily considered a 5-HT1B/1D agonist so triptans such as Zolmitriptan are suggested to act on the trigeminovascular system via peripheral as well as the central nervous system mechanisms.
Peripherally Triptans Cause the Following Processes:
They block the neurogenic inflammation occurring at the trigeminal vascular junction. It also causes the intracranial vessels through 5-HT1B to become vasoconstrictors. It also inhibits neuronal depolarization at the peripheral intracranial sites through 5-HT1B.
Centrally:
It is observed that the triptans inhibit the excitability of cells of the trigeminal nucleus caudalis through 5-HT1D agonism.
Pharmacokinetics:
Absorption:
Zolmitriptan was observed to be rapidly absorbed after administration via oral tablets and oral disintegrating tablets. It is stated to exhibit linear kinetics over the dose range from 2.5 milligrams (mg) to 50 mg. No substantial effect on the bioavailability of Zolmitriptan was observed because of food. Zolmitriptan shows quick action on the symptoms, and within 5 minutes of intranasal administration, Zolmitriptan can be detected in the brain. Zolmitriptan via the nasal route is absorbed quickly in comparison with Zolmitriptan via the oral route.
Distribution:
The mean of the apparent volume of distribution is estimated to be 7 L/kg whereas the plasma protein binding of Zolmitriptan is calculated to be 25 percent.
Metabolism:
Zolmitriptan is broken down into three metabolites with the help of human hepatic cytochrome P450 enzymes, primarily CYP1A 2. The next 2-third of the parent compound splits into an active metabolite N-desmethyl- Zolmitriptan (183C91); also, at that time, the remaining one-third divides into 2 inactive metabolites, such as Zolmitriptan N-oxide and an indole acetic acid derivative. The metabolite named N-desmethyl- Zolmitriptan is involved strongly in the overall effect of Zolmitriptan after its administration. This happens due to the metabolite’s 5HT1B/1D has a higher potency by 2 to 6 times that of the Zolmitriptan. But the pharmacokinetics of the N-desmethyl metabolite is almost the same as the pharmacokinetics of Zolmitriptan in the case of all nasal spray doses. The N-desmethyl metabolite can be detected in the plasma after the initial 15 minutes and the peak plasma concentration is observed within 3 hours after administration. The metabolic activation of Zolmitriptan is done by the CYP2D6 enzyme primarily. Zolmitriptan metabolization occurs into an alpha beta-unsaturated imine intermediate by CYP2D6.
Excretion:
The elimination half-life of Zolmitriptan is approximately three hours. Renal elimination helps in its excretion. The clearance rate is more than the glomerular filtration rate which indicates some renal tubular secretion of the drug.
Toxicology:
Zolmitriptan toxicity could not cause life-threatening complications in pediatric cases, but common signs of toxicity occurred, such as tachycardia, dyspnea, and vomiting. In adults, the overdose of Zolmitriptan caused hypertension, tachycardia, and drowsiness. A few cases of liver toxicity could also be seen due to the use of Zolmitriptan. There is always a risk of getting medication overdose headaches, which can be prevented if the patient is well-educated about the administration and use of the medication.
What Are the Drug Warning and Precautions of Zolmitriptan?
A few warnings and precautions are mentioned below, the physician need to consider before prescribing Zolmitriptan:
Hepatic enzymes can metabolize Zolmitriptan and thus patients should be prescribed a reduced dose of daily uptake because this procedure can alter the pharmacokinetics of the drug Zolmitriptan. The dose of Zolmitriptan should be reduced and adjusted in patients suffering from a severe hepatic impairment, as according to the instructions that come along with the drug, after the administration of Zolmitriptan, the blood concentration of the Zolmitriptan was raised in patients with moderate to severe hepatic impairment. Dose adjustment should be considered in severe renal impairment also as clearance of Zolmitriptan is reduced by 25 % in patients with severe renal impairment.
As not enough data is provided regarding the developmental problems occurring because of Zolmitriptan administration during pregnancy, alternative medicines should be given to the patient. A few shreds of evidence suggested that the Zolmitriptan level in the breast milk is mostly low, and the amount ingested by the infant is almost equal to none and cannot be seen as affecting the nursing infant. Zolmitriptan is also contraindicated in patients with cardiovascular diseases such as angina, myocardial infarction, and myocardial ischemia. The administration of Zolmitriptan may lead to arrhythmic conditions such as ventricular tachycardia and ventricular fibrillation, which can be life-threatening or fatal to the patient. A cardiac evaluation should be performed on the patient if any cardiovascular condition or disease is suspected. Overuse of migraine headache medications should be prevented, as it may lead to the worsening of the condition. Detoxification and withdrawal of these medicines should be monitored. More research is being carried out to study and observe further precautions to be taken in certain conditions.
Indications and Uses:
Food and Drug Administration-approved indications are mentioned below:
In adults, Zolmitriptan taken orally is used for the acute treatment of migraine with aura and also migraine without aura. The Zolmitriptan spray, which is taken through the nasal route can be used to treat acute migraine occurring in pediatric patients aged 12 or more than that and also adults.
Off-label Clinical Uses Are Mentioned Below:
Through nasal spray, acute treatment can be given for cluster headaches. Acute treatment in the case of menstrual migraine can be done with Zolmitriptan.
Dosage Strength and Forms:
2.5-Milligram Tablets:
These are yellowish in color, biconvex, round, coated with a film that identifies with “ Zolmitriptan” and 2.5 is debossed unilaterally. These are functionally scored.
5 Milligram Tablets:
These are pink, biconvex, and round, coated with a film that identifies them as “Zolmitriptan” and 5 mg is debossed unilaterally. These tablets are not functionally scored.
2.5-Milligram Oral Disintegrating Tablets:
These are white in color, flat-faced, round, uncoated, and beveled, and “Z” is debossed on one side. These tablets are not functionally scored.
5 Milligram Oral Disintegrating Tablets:
These are white colored, round, uncoated, and beveled, also “Z” and 5 debossed on one side. These tablets are not functionally scored.
Dosage and Administration:
Dosage:
The recommended starting dosage of Zolmitriptan is 1.25 milligrams or 2.5 milligrams. The 1.25 milligrams can be obtained by splitting the 2.5-milligram tablet in half. The maximum dosage recommended is 5 milligrams. If the migraine headache does not go away by 2 hours after the administration of Zolmitriptan or reoccurs after an improvement, then a second dose can be given to the patient, but it needs to be made sure that the second dose is given to the patient after 2 hours from the first dose. Not more than a daily dose of 10 mg in a 24-hour period should be advised.
What Are the Administration Considerations for Zolmitriptan?
The patients should be instructed that the oral disintegrating tablets should not be cut in half, as these are not functionally scored. The administration of these tablets does not require liquid to swallow. The packaging of the tablets should be opened only when the patient is ready to take the dose. The blister should be opened, and the tablet can be directly placed on the tongue. The tablet gets dissolved and swallowed with the help of saliva. The tablet should be stored away from moisture and light and at a certain temperature.
The dosage prescribed for patients with hepatic impairment should not exceed 5 milligrams per day. The recommended dose for patients with moderate to severe hepatic impairment is 1.25 milligrams which can be obtained by splitting the 2.5 milligrams tablets in half. The orally disintegrating tablets are contraindicated in such patients as they cannot be split in half as they are not functionally scored.
If Zolmitriptan is administered along with Cimetidine then the dosage should be 2.5 milligrams in a single dose, and the dosage should not exceed 5 milligrams in a 2 to 4 hours period of time.
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Considerations for Administration:
The oral tablets of Zolmitriptan that are functionally scored can be split in half to achieve the desired dose, but the orally disintegrating tablets of Zolmitriptan cannot be cut in half as they are not functionally scored. The blister packaging should be opened only when the patient is ready to take the dose, and after opening the blister packaging, the tablet can be directly placed on the tongue, where it gets dissolved and swallowed with the help of saliva. Any liquid, such as water, is not required while administering the drug. They should be stored away from light and moisture and at an appropriate temperature.
Contraindications:
If hypersensitivity is present to Zolmitriptan which may increase the risk of angioedema and anaphylaxis, Zolmitriptan should be avoided. The drug is also contraindicated in patients suffering from cerebrovascular or cardiovascular diseases, as 5-HT1B receptors are present in the coronary arteries. For example, diseases like myocardial infarction, prinzmetal angina, stroke, peripheral vascular disease, etc. In the case of coronary artery disease, the prescribing of Zolmitriptan should be avoided. For syndromes like Wolff-parkinson-white syndrome or arrhythmias seen in association with cardiac accessory conduction pathway disorders, Zolmitriptan should be prohibited. Conditions in which Zolmitriptan should be contraindicated are ischemic bowel diseases, uncontrolled hypertension, hemiplegic or basilar type of migraine, etc.
Clinical Trials:
In the acute treatment of migraine headaches, the efficacy of Zolmitriptan tablets was demonstrated in randomized, double-blind, placebo-controlled trials. In the initial study, patients were treated in a clinical set-up. In other studies, patients were treated as outpatients for their migraine headaches. In a few other studies, the patients who were previously given sumatriptan were excluded. Patients involved in these trials were mostly women and Caucasians, with a mean age of 40. The reduction in the severity of headache from severe and moderate to mild or no pain was achieved in the trials initially after 1 hour, 2 hours, and in most cases after 4 hours after the dose was given.
Associated symptoms with the migraine headache, such as nausea and increased sensitivity to light and sound, were also observed in the patients. The patient's responses were kept under surveillance for 24 hours after the dose was administered. If the migraine headache persisted or was recurrent, in such cases, the second dose was advised, but after 2 hours from the administration of the first dose. The window for taking the dose for recurrent migraine headaches was 2 to 4 hours. The efficacy of Zolmitriptan was not affected by the presence of aura, menstrual cycle, duration of headache, age, gender, weight of the patient, etc.
Drug Interactions:
The observation of drug interactions was carried out in healthy patients with 10 milligrams of Zolmitriptan and a single dose of other medicines. A few examples are mentioned below:
MAO Inhibitors:
After one week of administration of Moclobemide, a specific MAO-A inhibitor, an increase in the Cmax and area under the curve (AUC) for Zolmitriptan was seen at about 25 percent and three times the increase in the Cmax and AUC of the activated N-desmethyl metabolites of Zolmitriptan. MAO inhibitors are not indicated for Zolmitriptan patients. Selegiline, which is a selective MAO-B inhibitor, was given to the patients at a dose of 10 milligrams per day for 1 week, no effect on the pharmacokinetics of Zolmitriptan and its metabolite was seen.
Cimetidine:
After the administration of cimetidine, it was observed that the half-life and the AUC of Zolmitriptan and its metabolite were approximately doubled.
Oral Contraceptives:
In the analysis of the pharmacokinetic data amongst all the studies carried out, it was observed that the mean Cmax and AUC of Zolmitriptan were increased by 30 percent to 50 percent and T max was delayed by one and a half hours in women taking oral contraceptives. The impact of Zolmitriptan on the pharmacokinetics of oral contraceptives needs to be studied.
Acetaminophen:
A single dose of 1 gram of acetaminophen did not compromise the pharmacokinetics of Zolmitriptan and the N-desmethyl metabolite, but the administration of Zolmitriptan delayed the Tmax of acetaminophen by an hour.
Other Specifications:
Use of Zolmitriptan in Pregnant Women:
There are not enough well-carried studies on pregnant women, which is why Zolmitriptan can be used for pregnant women only if the incidence of benefits is more than the potential risk to the fetus. Alternative medications to Zolmitriptan can also be advised in pregnancy.
Use of Zolmitriptan in Lactating Mothers:
There is no evidence to state the excretion of Zolmitriptan in human milk. Many drugs can be observed to be excreted in human milk, and hence, as there is a chance of any adverse reactions occurring, the decision to continue nursing the infant or to stop nursing should be taken as per the need of the drug for the mother.
Use in Pediatric Patients:
The use or after-administration effects of Zolmitriptan in the pediatric patients have not been studied. The administration of Zolmitriptan in patients below 18 years of age is contraindicated.
