Rizatriptan
Serotonin agonist for acute treatment of migraine attacks
Rizatriptan is a selective serotonin 5-HT1B/1D agonist from the triptan group, approved for the acute treatment of migraine attacks with and without aura. In many countries it is available under the brand name Maxalt as well as numerous generics. Rizatriptan is offered as a conventional tablet and as a wafer (Maxalt MLT), which allows a rapid onset of action even without water and facilitates intake in the presence of migraine-related nausea.
Rizatriptan is considered one of the faster and more potent triptans and has led to pain freedom or significant pain reduction within two hours in the majority of patients in clinical studies. It acts exclusively against an acute migraine attack and is not suitable for prophylaxis. In comparative studies, rizatriptan at the standard dose of 10 mg showed higher efficacy than sumatriptan 100 mg with a comparable safety profile.
Mechanism of Action
Rizatriptan binds selectively to serotonin receptors of the 5-HT1B and 5-HT1D subtypes. These receptors are located on the blood vessels of the meninges and on presynaptic nerve endings of the trigeminal nerve. Activation of the 5-HT1B receptors causes vasoconstriction of the extracranial meningeal and carotid vessels, which are pathologically dilated during a migraine attack. Normalisation of this vasodilation contributes significantly to pain reduction.
Activation of the 5-HT1D receptors at the presynaptic trigeminal endings inhibits the release of pro-inflammatory neuropeptides such as substance P and calcitonin gene-related peptide (CGRP). These neuropeptides play a central role in neurogenic inflammation of the meninges, which contributes to the typical throbbing migraine pain. By inhibiting their release, trigeminovascular activation is reduced and the pain impulse is interrupted.
Rizatriptan thus acts at two sites of the migraine pathomechanism simultaneously: it normalises pathological vasodilation and interrupts neurogenic inflammation at the trigeminal nerve, which explains its rapid and effective onset of action.
Indications
- Acute therapy of migraine with aura: Administration at the onset of the headache phase (after the aura subsides) or in the aura phase if previously indicated by the physician
- Acute therapy of migraine without aura: Administration at the onset of the migraine attack; the earlier in the attack, the better the efficacy
- Menstrual migraine: Rizatriptan is also effective in hormonally triggered migraine attacks
Rizatriptan is intended solely for acute therapy. Use for migraine prophylaxis is not approved and not appropriate.
Dosage and Administration
Adults: 10 mg as a single dose at the onset of the migraine attack. The 5 mg dose is intended for patients who are simultaneously taking propranolol (as propranolol significantly increases rizatriptan levels). Second dose: If the attack initially responds to the first dose of 10 mg but returns within 24 hours, a second dose may be taken. The minimum interval between two doses is 2 hours. Maximum daily dose: 20 mg. Children and adolescents (12 to 17 years): 5 mg; taking 10 mg has not been shown to be significantly better and is associated with more side effects.
Rizatriptan tablets are taken with liquid; wafers are allowed to dissolve on the tongue (no water required). The wafer contains aspartame (phenylalanine source), which must be noted in phenylketonuria. Rizatriptan should not be taken preventively; intake on more than 10 days per month leads to medication-overuse headache.
Side Effects
Very common: Dizziness, somnolence (drowsiness), nausea, a feeling of heaviness, pressure or tightness in the chest, throat or neck. The so-called "triptan sensation" (chest tightness, tingling in arms and legs, warmth) is a known and common effect that is harmless and arises from vasoconstriction, but can alarm patients.
Common: Headache (as rebound after the effect wears off), fatigue, dry mouth, weakness, hot sensation, numbness, shortness of breath, palpitations, dyspepsia, diarrhoea.
Rare to very rare: Tachycardia, cardiac arrhythmias, hypertensive crises, coronary spasms, myocardial infarction (in patients with cardiovascular pre-existing conditions); serotonin syndrome (particularly in combination with serotonergic substances).
Drug Interactions
Propranolol: Doubles the plasma levels of rizatriptan by inhibiting MAO-A-mediated degradation. When taking propranolol concurrently (e.g. for migraine prophylaxis), the rizatriptan dose should be reduced to 5 mg.
MAO inhibitors (moclobemide, selegiline, rasagiline, tranylcypromine): Greatly elevated rizatriptan levels; combination is contraindicated. After discontinuing irreversible MAO inhibitors, a minimum interval of 14 days must be observed.
Other triptans and ergotamine: Additive vasoconstrictive effect; no concurrent intake and at least 24 hours interval to other triptans or ergotamine preparations.
SSRIs, SNRIs, lithium, linezolid, tramadol: Increased risk of serotonin syndrome (combination with caution and medical monitoring).
St John's Wort: Induction of CYP metabolism and serotonin synergy; concurrent intake not recommended.
Special Notes
Cardiovascular contraindications: Rizatriptan is contraindicated in patients with coronary artery disease (CAD), previous myocardial infarction or stroke, transient ischaemic attack (TIA), angina pectoris (including Prinzmetal angina), peripheral arterial occlusive disease and uncontrolled hypertension. Triptans should only be used in at-risk patients before initial use following cardiological evaluation.
Pregnancy: Adequate controlled data on the safety of rizatriptan in pregnancy are not available. For migraine attacks in pregnancy, preferred agents such as paracetamol (in the first and second trimester) should be used; triptans only after careful benefit-risk assessment. Rizatriptan is detectable in breast milk; breastfeeding should be suspended for 24 hours after intake.
Avoiding medication-overuse headache: Taking triptans or other pain medications on more than 10 days per month leads to medication-induced chronic headache. Patients with frequent attacks should consider migraine prophylaxis.
Hemiplegic or basilar migraine: Rizatriptan is contraindicated in these rare forms of migraine.
Frequently Asked Questions
When should rizatriptan be taken, best during the aura or at the pain?
Rizatriptan works best when taken at the onset of the headache phase. In migraine with aura, it is advisable to take it after the aura has subsided and at the first appearance of the headache, since triptans are less effective in the aura and do not shorten the aura duration. In migraine without aura: the earlier in the attack, the better.
What to do if rizatriptan does not work?
If rizatriptan has not shown sufficient effect after 2 hours, a second dose should not be taken, as the first dose was also ineffective. In this case, NSAIDs (ibuprofen, naproxen) or paracetamol can be used as alternatives. The next time you see your doctor, discuss a triptan change or combination therapy.
Is rizatriptan available only on prescription?
Yes, rizatriptan is prescription-only and is only dispensed on medical prescription. A medical diagnosis of migraine and exclusion of possible contraindications is mandatory before use.
References
- Summary of Product Characteristics Maxalt (MSD), as of 2024
- German Migraine and Headache Society (DMKG): Guideline for the Treatment of Migraine, 2022
- Tfelt-Hansen P et al.: Rizatriptan vs other triptans in the acute treatment of migraine: a systematic review. Cephalalgia, 2006
- European Medicines Agency (EMA): Maxalt EPAR
- Headache Classification Committee of the International Headache Society (IHS): ICHD-3, 2018