rizatriptan

Action and Spectrum

Actions and Spectrum: 

• The mechanism of action of rizatriptan involves several different pathways, including stimulation of serotonin receptors, inhibition of calcitonin gene-related peptide (CGRP), and reduction of the release of pro-inflammatory neuropeptides. 
• rizatriptan has a broad spectrum of activity and can treat a wide range of migraine headaches, including those with and without aura. It is effective for treating moderate to severe migraines and can relieve symptoms such as headache pain, nausea, and sensitivity to light and sound. However, it is essential to note that rizatriptan is inadequate for preventing migraines or treating other types of headaches. It should not be used to treat headaches caused by other underlying conditions. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Fatigue (13-30%, dose-related) 

Drowsiness (13-30%, dose-related) 

Dizziness (11-15%)  

1-10% 

Somnolence (4-8%) 

Nausea (4-6%) 

Hot flashes (1-5%) 

Dry mouth (3%) 

Pain/pressure in chest, neck, throat, and jaw (<2%) 

Dyspnea (>1%) 

Palpations (>1%) 

Dizziness (4-9%) 

Fatigue (4-7%; dose-related) 

Asthenia (1-5%) 

Paresthesia (3-4%) 

Chest pain (2-3%) 

Headache (<2%) 

Hypoesthesia (>1%) 

Skin flushing (>1%)  

<1%  

Angioedema 

Hypertensive crisis 

Hallucination 

Hearing impairment 

Tachycardia 

Wheezing 

Bradycardia 

Epidermal necrolysis 

Arrhythmias 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: rizatriptan is contraindicated in patients with known hypersensitivity or allergy to the drug. 
• Ischemic heart disease: rizatriptan should not be used in patients with ischemic heart disease or a history of myocardial infarction, angina, or coronary artery vasospasm. 
• Uncontrolled hypertension: rizatriptan can cause an increase in blood pressure and, therefore, should not be used in patients with uncontrolled hypertension. 
• Severe hepatic impairment: rizatriptan is metabolized by the liver and should be used cautiously or avoided in patients with severe hepatic impairment. 
• Use with MAO inhibitors: rizatriptan should not be used within two weeks of discontinuing a monoamine oxidase (MAO) inhibitor or in patients taking MAO inhibitors. 
• Peripheral vascular disease: rizatriptan should not be used in patients with peripheral vascular disease, including ischemic bowel disease. 
• Severe renal impairment: rizatriptan should be used cautiously or avoided in patients with severe renal impairment. 

Caution: 

• Cardiovascular disease: rizatriptan can cause an increase in blood pressure and heart rate and, therefore, should be used with caution in patients with cardiovascular disease, including those with a history of stroke, transient ischemic attack, or peripheral vascular disease. 
• Hepatic impairment: rizatriptan is metabolized by the liver and, therefore, should be used cautiously in patients with mild to moderate hepatic impairment. 
• Renal impairment: rizatriptan should be used cautiously in patients with mild to moderate renal impairment. 
• Pregnancy and breastfeeding: The safety of rizatriptan use during pregnancy and breastfeeding is not well established, and therefore it should be used with caution in these populations. 
• Elderly: Elderly patients may be more sensitive to the effects of rizatriptan and, therefore, should be started on a lower dose and monitored closely for adverse effects. 
• Medications: rizatriptan can interact with other medications, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and triptans. Patients should inform their healthcare provider of all medications before starting treatment with rizatriptan. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

rizatriptan is a selective serotonin 5-HT1B/1D receptor agonist, which binds to specific serotonin receptors in the brain and activates them. By binding to these receptors, rizatriptan can cause constriction of blood vessels in the brain and decrease the release of inflammatory substances that can trigger migraine headaches. 

Pharmacodynamics: 

• The pharmacodynamics of rizatriptan involve its interaction with specific serotonin receptors in the brain, which leads to its therapeutic effects in treating migraines. 
• rizatriptan is a selective agonist of the 5-HT1B and 5-HT1D serotonin receptors in the brain’s blood vessels and nerves. By binding to these receptors, rizatriptan causes vasoconstriction of the blood vessels in the brain. It inhibits the release of neuropeptides and other substances involved in the pain and inflammation associated with migraines. 
• rizatriptan also has an inhibitory effect on trigeminal nerve activity, which is thought to contribute to the pain and other symptoms of migraines. By reducing the activity of these nerves, rizatriptan can help relieve the pain, nausea, and sensitivity to light and sound associated with migraines. 

Pharmacokinetics: 

Absorption 

rizatriptan is well absorbed after oral administration, with a 45-50% bioavailability. Food can delay the absorption of rizatriptan, but this does not significantly affect its overall effectiveness.  

Distribution 

rizatriptan has a moderate volume of 110-140 L distribution, and it is approximately 14% protein-bound. The drug can cross the blood-brain barrier and has high lipid solubility.  

Metabolism 

rizatriptan is extensively metabolized in the liver by the cytochrome P450 enzyme system, primarily through the CYP3A4 isoenzyme. The primary metabolite of rizatriptan is N-monodesmethyl-rizatriptan, which is pharmacologically inactive.  

Elimination and Excretion 

rizatriptan and its metabolites are eliminated mainly in the urine, with approximately 82% of the dose excreted unchanged. A small amount of the drug and its metabolites are also excreted in the feces. 

Adminstartion

Administration: 

• rizatriptan is available in tablet form for oral administration. The tablets should be swallowed whole with water and taken with or without food. The recommended dose of rizatriptan for adults is 5 mg or 10 mg, with a maximum daily dose of 30 mg. 
• If the initial dose does not adequately relieve migraine symptoms, a second dose may be taken at least 2 hours after the first dose. However, the maximum daily dose should not exceed 30 mg. 
• It is important to note that rizatriptan is not adequate for the prevention of migraines or the treatment of other types of headaches. The drug should only be used to treat migraines and is not recommended for use in children or adolescents under 18. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: rizatriptan 

Pronunciation: [ RYE-za-TRIP-tan ] 

Why do we use rizatriptan? 

• rizatriptan is a medication used for the acute treatment of migraines with or without aura in adults. A migraine is a severe headache characterized by throbbing pain, often on one side of the head, and may be accompanied by nausea, vomiting, and sensitivity to light and sound. 
• rizatriptan belongs to a class of drugs called triptans, which work by binding to serotonin receptors in the brain and reducing inflammation and constriction of blood vessels. This action helps to relieve the symptoms of migraines, such as headache pain, nausea, and sensitivity to light and sound.