Zolmitriptan is a selective agonist for serotonin 5-HT-1B and 5-HT-1D receptors that are present in the cranial arteries and sensory nerves of the trigeminal system. [select-faq faq_id='7198'] It is indicated for the treatment of the following disorders:

• For the acute treatment of migraine with or without aura in adults and children aged 12 years or more

• Off Label Uses of Zolmitriptan in Adults include:

  • Treatment of Cluster headache

  • For the short-term prevention of menstrual migraines

Zolmitriptan Dose in Adults

Dose as off-label use in the treatment of Cluster headache:

• Nasal inhalation or oral tablets:
  • The usual dose is 5 - 10 mg at the onset of cluster headache up to a maximum single dose of 10 mg.

Dose in the treatment of Migraine:

• Nasal inhalation:
  • 2.5 mg to the maximum single dose of 5 mg
• Tablet:
  • 1.25 - 2.5 mg orally to a maximum single dose of 5 mg
• Orally disintegrating tablet:
  • 2.5 mg orally to a maximum single dose of 5 mg
  • A second dose may be repeated in 2 hours up to a maximum dose of 10 mg/day if the patient does not respond to the first dose or the headache returns after transient improvement.

Dose as off-label use in the prophylaxis of Menstrual migraine:

• 5 mg orally 2 - 3 times a day.
• It should be started 2 days before the onset of menstrua cycles and continued for up to 5 days after the onset of menses for a total of seven days.

• Dosing adjustment for concomitant therapy with cimetidine:

  • A maximum single dose of 2.5 mg or 5 mg per day should not be exceeded.

Zolmitriptan Dose in Childrens

Dose in the treatment of Migraine in children:

• Children older than 12 years and Adolescents:
  • Intranasal administration:
    • 2.5 mg initially.
    • The dose may be titrated based on the patient's response to a maximum single dose of 5 mg.
    • It should be administered at the onset of symptoms.
    • A second dose may be repeated in 2 hours up to a maximum dose of 10 mg/day if the patient does not respond to the first dose or the headache returns after transient improvement.

• Dosing adjustment for concomitant therapy with cimetidine:

  • A maximum single dose of 2.5 mg or 5 mg per day should not be exceeded.

Pregnancy Risk Factor: C

• It is not known if any data are available.
• This should be avoided, and other agents should be used.
• Particularly if adverse fetal outcomes are observed, inadvertent exposure should also be reported.

Zolmitriptan use during breastfeeding:

• Excretion of the drug into breastmilk is not known.
• The manufacturer advises weighing the benefits and risks of its use in both the infant and the nursing mother.
• Other safer agents should be preferably used.

Zolmitriptan dose in Kidney disease:

The manufacturer does not recommend any dose adjustment in patients with kidney disease, however, clearance is impaired with a CrCl of less than 25 ml/min. 

Zolmitriptan dose in Liver disease:

Tablet formulation:

• Mild impairment:
  • No adjustment in the dose is required.
• Moderate to severe impairment:
  • Initiate therapy with 1.25 mg to a maximum daily dose of 5 mg in severe hepatic impairment.

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Orally disintegrating tablet:

• Mild impairment:
  • No adjustment in the dose is required.
• Moderate to severe impairment:
  • Avoid its use.

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Nasal inhalation:

• Mild impairment:
  • No adjustment in the dose is necessary.
• Moderate to severe:
  • Avoid its use.

Common Side Effects of Zolmitriptan Include:

• Gastrointestinal:
  • Unpleasant taste

Less Common Side Effects of Zolmitriptan Include:

• Cardiovascular:
  • Chest Pain
  • Chest Pressure
  • Facial Edema
  • Palpitations
  • Cardiac Arrhythmia
  • Hypertension
  • Syncope
  • Tachycardia
• Central Nervous System:
  • Dizziness
  • Paresthesia
  • Drowsiness
  • Local Alterations In Temperature Sensations
  • Sensation Of Pressure
  • Hyperesthesia,
  • Flushing Sensation
  • Pain
  • Vertigo
  • Chills
  • Depersonalization
  • Headache
  • Agitation
  • Amnesia
  • Anxiety
  • Depression
  • Emotional Lability
  • Insomnia
  • Nervousness
• Dermatologic:
  • Diaphoresis
  • Pruritus
  • Skin Rash
  • Urticaria
• Gastrointestinal:
  • Nausea
  • Xerostomia
  • Dyspepsia
  • Dysphagia
  • Abdominal Pain
  • Vomiting
• Genitourinary:
  • Urinary Frequency
  • Urinary Urgency
• Hypersensitivity:
  • Hypersensitivity Reaction
• Local:
  • Local Pain
  • Application Site Irritation
• Neuromuscular & Skeletal:
  • Weakness
  • Arthralgia
  • Myalgia
• Otic:
  • Tinnitus
• Renal:
  • Polyuria
• Respiratory:
  • Nasal Discomfort
  • Constriction Of The Pharynx
  • Pressure On Pharynx
  • Bronchitis
  • Cough
  • Dyspnea
  • Epistaxis
  • Laryngeal Edema
  • Pharyngitis
  • Rhinitis
  • Sinusitis

Contraindication to Zolmitriptan Include:

• Allergy reactions to zolmitriptan and any component of the formulation
• Angina pectoris, myocardial injury, or history of myocardial injury, is an example of ischemia.
• Vasospasm of the Coronary Artery, including Prinzmetal-type angina
• Wolff-Parkinson-White syndrome or arrhythmias secondary to cardiac accessory conduction pathway
• Peripheral Vascular Disease
• Ischemic bowel disease
• Hypertension uncontrolled
• Concomitant with another 5-HT agonist, ergotamine-containing or ergot-type medication like dihydroergotamine or methysergide
• History of stroke, transient ischemic attacks, or basilar, hemiplegic, or ophthalmoplegic headaches.
• Use of monoamine-oxidase A (MAO) inhibitors in combination with zolmitriptan within 14-days of stopping MAO-A inhibitor therapy.
• Heart disease of the valvular kind

Warnings and Precautions

• Cardiac events:
  • Zolmitriptan can cause vasoconstriction.
  • It may lead to Coronary artery vasospasm and myocardial injury, ischemia, myocardial ischemia, ventricular arrhythmias such as fibrillation and ventricular tachycardia, cardiac arrest and even death.
  • Patients suffering from vasospastic or coronary artery disease should not use it.
  • Likewise, patients with Prinzmetal's variant angina, WPW (Wolff-Parkinson-White) Syndrome, and those with conduction defects should also avoid using it.
  • Patients with chest pain or tightness symptoms should be evaluated by a physician. If the patient is not responding to treatment, he/she may be asked to stop taking medication.
• Cerebrovascular events
  • Zolmitriptan has been linked to strokes and subarachnoid hemorhage in the brain.
  • Patients who have suffered from stroke or TIA should not use it.
• High blood pressure
  • Zolmitriptan should not be prescribed to patients with uncontrolled hypertension.
  • Patients with hypertension controlled and sometimes those without a history of hypertension can experience a significant increase in blood pressure, including hypertensive crisis.
• Vasospasm-related events
  • It has been associated with Vasospastic episodes, including gastrointestinal vascular and peripheral ischemia.
  • Infarctions presenting with bloody diarrhea, abdominal pain, and splenic injury, as well as Raynaud syndrome, have been reported.
  • Patients who have clinical signs that suggest a vasospastic disorder should receive the lowest dose possible.
• Visual effects
  • It has been reported that temporary (rarely permanent!) visual impairments have been caused by its use.
• Coronary artery disease
  • Patients at high risk for coronary artery disease should not be given the drug.
  • These patients are at high risk for developing CAD:
    • Hypertension
    • Hypercholesterolemia
    • Smoker
    • Obesity
    • Diabetes
    • Strong family history of coronary heart disease
    • Menopause
    • Males over 40 years old are considered older.
  • It is important to evaluate patients who have been diagnosed with coronary artery disease before administering the medication. The first dose should be administered in a hospital.
  • Regular evaluations of patients should be done for CAD.
• Hepatic impairment
  • Patients with hepatic impairment need to be cautious as drug clearance can be impaired in patients suffering from liver disease.
  • Patients with liver disease should not use the nasal spray or the oral disintegrating tablets.
  • Patients with severe or moderate hepatic impairment may need to adjust the dose of their oral tablets.

Zolmitriptan: Drug Interaction

Monitor:

• The severity of the headache.
• Clinical features of angina especially in patients at risk.
• Blood pressure in hypertensive patients.
• ECG in patients at risk (with the first dose )

How to administer Zolmitriptan?

• It should be administered immediately the migraine symptoms are apparent.
• TheTabletIf a lower initial dose is needed, the dosage can be divided in half.
• TheOrally-disintegrating tabletIt must be consumed whole. It must not be broken or crushed.
•  It should not be mixed with liquids. However, it can be placed on the tongue to dissolve.
• Before you use the nasal sprayGently blow your nose. 
• Remove the protective cap, and instill the device directly into the nostril. 
• Block the opposite nostril, and inhale gently while pushing the plunger of this device. 

Mechanism of action of Zolmitriptan:

• It acts as a selective antagonist for serotonin 5-HT-1B or 5-HT-1D receptors, which are found in the cranial vessels and sensory nerves of trigeminal systems.
• It decreases inflammation due to antidromic neural transmission, and causes vasoconstriction. This can relieve the symptoms of migraine.

It is well absorbed.

25% of the drug is protein-bound.

It is metabolized to the more active compound N-N-desmethyl metabolite.

It has been abioavailabilityAfter oral intake, the average bioavailability of the nasal spray is 40% The nasal spray has a higher mean bioavailability than the oral tablet (102%).

It has been a half-life eliminationapproximately 3 hours, and the time topeak serum concentrationThe oral tablet takes approximately 1.5 hours to complete.

60-65% of the drug areexcretedIt is found in the urine, and 30% of it is excreted by the feces.

International Brands of Zolmitriptan:

• AG-Zolmitriptan
• APO-Zolmitriptan
• APO-Zolmitriptan Rapid
• CCP-Zolmitriptan
• DOM-Zolmitriptan
• JAMP-Zolmitriptan
• JAMP-Zolmitriptan ODT
• Mar-Zolmitriptan
• MINT-Zolmitriptan
• MINT-Zolmitriptan ODT [DSC]
• MYLAN-Zolmitriptan ODT [DSC]
• MYLAN-Zolmitriptan [DSC]
• NAT-Zolmitriptan
• PMSZolmitriptan
• PMS-Zolmitriptan ODT
• RIVA-Zolmitriptan [DSC]
• SANDOZ Zolmitriptan
• SANDOZ Zolmitriptan ODT
• Septa Zolmitriptan-ODT
• TEVA-Zolmitriptan
• TEVA-Zolmitriptan OD
• VANZolmitriptan ODT
• Zomig
• Zomig Rapimelt
• Ascotop
• Emicrania
• Heng Li An
• Miotrol
• Myslee
• Nomi
• Olatrip
• Rapimig
• Zolan
• Zolmigo
• Zolmigren
• Zolmiles
• Zolmist
• Zolmit
• Zoltrip
• Zomig
• Zomig Rapimelt
• Zomig ZMT
• Zomigon
• Zomigoro
• Zomiles
• Zomitan

Zolmitriptan in Pakistan: