RIZAT

Indications

• Acute migraine treatment

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Initially 10 mg, taken as soon as possible after migraine onset. A second dose of 10 mg may be taken after 2 hours if required, but only if the migraine recurs. The maximum daily dose is 20 mg.

Mechanism of action

Rizatriptan acts as a selective agonist at the 5-HT1B and 5-HT1D receptors located on intracranial blood vessels and trigeminal sensory nerves. Activation of these receptors leads to vasoconstriction of extracerebral blood vessels and inhibition of pro-inflammatory neuropeptide release, which are key factors in the pathophysiology of migraine. Additionally, rizatriptan modulates trigeminal neuronal activity, thereby reducing migraine pain.

Pharmacodynamics

Rizatriptan demonstrates a rapid onset of action, achieving maximum plasma concentrations quickly and providing faster relief compared to other triptans. It can cause transient increases in blood pressure, though it is not associated with significant risk of myocardial ischemia in patients with normal coronary circulation. Rizatriptan shows a weak affinity for other serotonin receptor subtypes and lacks significant activity at adrenergic, dopaminergic, and other receptor systems, highlighting its targeted action in migraine relief.

Pharmacokinetics

Rizatriptan is well absorbed after oral administration, with a relatively short elimination half-life compared to other triptans. It undergoes hepatic metabolism, primarily via monoamine oxidase, and is eliminated from the body through renal excretion. The pharmacokinetic profile supports its use as a rapid-acting agent for acute migraine treatment.

Contra-indications

• Severe hypertension
• Uncontrolled hypertension
• Conditions which predispose to coronary artery disease
• Concurrent use with ergotamine

Adverse effects

• Dizziness
• Drowsiness
• Nausea
• Dry mouth
• Fatigue
• Headache
• Palpitations
• Musculoskeletal stiffness
• Insomnia
• Vomiting
• Taste altered
• Tremor
• Blurred vision
• Hypertension
• Asthenia
• Diarrhoea
• Anxiety
• Skin reactions
• Syncope
• Angioedema
• Arrhythmias
• Ataxia
• Disorientation
• Dyspnoea
• Facial edema
• Hyperhidrosis
• Myalgia
• Muscle weakness
• Wheezing
• Seizure
• Serotonin syndrome
• Toxic epidermal necrolysis

Interactions

• Severe interaction with moclobemide (increases exposure)
• Unknown interaction with propranolol (increases exposure)
• Unknown interaction with irreversible MAOIs (increases exposure)
• Unknown interaction with ergotamine (increases risk of vasoconstriction)

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor blood pressure in patients with hypertension
• Not licensed for use in elderly patients

Pregnancy

Rizatriptan should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, as data on safety in pregnancy is limited.

Breast-feeding

Rizatriptan is excreted in breast milk, and caution should be exercised when administering to nursing mothers.

Storage

Store below 25 degrees Celsius, protect from moisture and light.

Formulations

• Rizatriptan (as Rizatriptan benzoate) 5 mg tablets
• Rizatriptan (as Rizatriptan benzoate) 10 mg tablets

Mechanism of action

There are several physiological and molecular processes implicated in the pathophysiology of migraine. Vasodilation of intracranial extracerebral blood vessels, particularly those supplying the dura mater, has been associated with migraine pain. Activation of the trigeminovascular system leads to the release of vasoactive neuropeptides (such as substance P, calcitonin gene-related peptide (CGRP), and neurokinin A) from the trigeminal nerve innervating the intracranial vessels and dura mater. Vasoactive neuropeptides cause perivascular inflammation and vasodilation in the periphery. Migraine-associated nausea and vomiting are thought to arise from the activation of central and nociceptive sensory neurons that project to autonomic brain-stem nuclei and higher subcortical and cortical pain processing centres. An imbalance in serotonin (5-HT) levels has also been documented: 5-HT binds to 5-HT_1B and 5-HT_1D receptors to promote trigeminal neuronal firing and vasoconstriction. Rizatriptan is a selective agonist at the 5-HT_1B and 5-HT_1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system. It binds to these receptors with high affinity. The exact mechanism of action of rizatriptan has not been fully elucidated; however, several documented pharmacological actions of rizatriptan may contribute to its antimigraine effects. Rizatriptan causes vasoconstriction of intracranial extracerebral blood vessels, which is thought to occur primarily via 5-HT_1B receptors. Rizatriptan also inhibits nociceptive neurotransmission in trigeminal pain pathways. It attenuates the release of vasoactive neuropeptides by the trigeminal nerve, which is thought to occur via neurogenic and central 5-HT_1D receptors. Rizatriptan inhibited neurogenic dural vasodilation and plasma protein extravasation in animal studies.

Pharmacodynamics

Rizatriptan relieves migraine-associated symptoms. Rizatriptan is reported to reach the maximum plasma concentrations more quickly and produces a more rapid onset of pain relief than other triptans, such as [sumatriptan]; however, it has a relatively shorter elimination half-life than other triptans. Rizatriptan causes transient increases in blood pressure to some extent. _In vitro_, rizatriptan was shown to contract isolated human coronary arteries; however, since the EC₅₀ for this effect is high, rizatriptan is not expected to cause myocardial ischemia at therapeutic plasma concentrations in patients with normal coronary circulation. Rizatriptan has a weak affinity for other 5-HT1 receptor subtypes (5-HT_1A, 5-HT_1E, 5-HT_1F) and the 5-HT₇ receptor but has no significant activity at 5-HT₂, 5-HT₃, alpha- and beta-adrenergic, dopaminergic, histaminergic, muscarinic or benzodiazepine receptors.