Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire, EN11 9BU, UK
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
Concurrent administration of monoamine oxidase (MAO) inhibitors or use within two weeks of discontinuation of MAO inhibitor therapy (see section 4.5).
MAXALT is contra-indicated in patients with severe hepatic or severe renal insufficiency.
MAXALT is contra-indicated in patients with a previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA).
Moderately severe or severe hypertension, or untreated mild hypertension.
Established coronary artery disease, including ischaemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischaemia), signs and symptoms of ischaemic heart disease, or Prinzmetal’s angina.
Peripheral vascular disease.
Concomitant use of rizatriptan and ergotamine, ergot derivatives (including methysergide), or other 5-HT1B/1D receptor agonists (see section 4.5).
MAXALT should only be administered to patients in whom a clear diagnosis of migraine has been established. MAXALT should not be administered to patients with basilar or hemiplegic migraine.
MAXALT should not be used to treat ‘atypical’ headaches, i.e. those that might be associated with potentially serious medical conditions (e.g. CVA, ruptured aneurysm) in which cerebrovascular vasoconstriction could be harmful.
Rizatriptan can be associated with transient symptoms including chest pain and tightness which may be intense and involve the throat (see section 4.8). Where such symptoms are thought to indicate ischaemic heart disease, no further dose should be taken and appropriate evaluation should be carried out.
As with other 5-HT1B/1D receptor agonists, rizatriptan should not be given, without prior evaluation, to patients in whom unrecognised cardiac disease is likely or to patients at risk for coronary artery disease (CAD) [e.g. patients with hypertension, diabetics, smokers or users of nicotine substitution therapy, men over 40 years of age, post-menopausal women, patients with bundle branch block, and those with strong family history for CAD]. Cardiac evaluations may not identify every patient who has cardiac disease and, in very rare cases, serious cardiac events have occurred in patients without underlying cardiovascular disease when 5-HT1 agonists have been administered. Those in whom CAD is established should not be given MAXALT (see section 4.3).
5-HT1B/1D receptor agonists have been associated with coronary vasospasm. In rare cases, myocardial ischaemia or infarction have been reported with 5-HT1B/1D receptor agonists including MAXALT (see section 4.8).
Other 5-HT1B/1D agonists (e.g. sumatriptan) should not be used concomitantly with MAXALT (see section 4.5).
It is advised to wait at least six hours following use of rizatriptan before administering ergotamine-type medications (e.g. ergotamine, dihydro-ergotamine or methysergide). At least 24 hours should elapse after the administration of an ergotamine-containing preparation before rizatriptan is given. Although additive vasospastic effects were not observed in a clinical pharmacology study in which 16 healthy males received oral rizatriptan and parenteral ergotamine, such additive effects are theoretically possible (see section 4.3).
Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) has been reported following concomitant treatment with triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs). These reactions can be severe. If concomitant treatment with rizatriptan and an SSRI or SNRI is clinically warranted, appropriate observation of the patient is advised, particularly during treatment initiation, with dose increases, or with addition of another serotonergic medication (see section 4.5).
Undesirable effects may be more common during concomitant use of triptans (5-HT1B/1D agonists) and herbal preparations containing St John’s wort (Hypericum perforatum).
Angioedema (e.g. facial oedema, tongue swelling and pharyngeal oedema) may occur in patients treated with triptans, among which is rizatriptan. If angioedema of the tongue or pharynx occurs, the patient should be placed under medical supervision until symptoms have resolved. Treatment should promptly be discontinued and replaced by an agent belonging to another class of drugs.
The quantity of lactose monohydrate in each tablet is as follows: 30.25 mg in the 5 mg tablet and 60.50 mg in the 10 mg tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The potential for interaction should be considered when rizatriptan is administered to patients taking CYP 2D6 substrates (see section 4.5).
Prolonged use of any painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The diagnosis of MOH should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.
Due to an additive effect, the concomitant use of rizatriptan and ergotamine, ergot derivatives (including methysergide), or other 5-HT1B/1D receptor agonists (e.g. sumatriptan, zolmitriptan, naratriptan) increase the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contra-indicated (see section 4.3).
Rizatriptan is principally metabolised via monoamine oxidase, ‘A’ subtype (MAO-A). Plasma concentrations of rizatriptan and its active N-monodesmethyl metabolite were increased by concomitant administration of a selective, reversible MAO-A inhibitor. Similar or greater effects are expected with non-selective, reversible (e.g. linezolid) and irreversible MAO inhibitors. Due to a risk of coronary artery vasoconstriction and hypertensive episodes, administration of MAXALT to patients taking inhibitors of MAO is contraindicated (see section 4.3).
Plasma concentrations of rizatriptan may be increased by concomitant administration of propranolol. This increase is most probably due to first-pass metabolic interaction between the two drugs, since MAO-A plays a role in the metabolism of both rizatriptan and propranolol. This interaction leads to a mean increase in AUC and Cmax of 70-80%. In patients receiving propranolol, the 5 mg dose of MAXALT should be used (see section 4.2).
In a drug interaction study, nadolol and metoprolol did not alter plasma concentrations of rizatriptan.
There have been reports describing patients with symptoms compatible with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans (see section 4.4).
In vitro studies indicate that rizatriptan inhibits cytochrome P450 2D6 (CYP 2D6). Clinical interaction data are not available. The potential for interaction should be considered when rizatriptan is administered to patients taking CYP 2D6 substrates.
Effects on human fertility have not been investigated. Animal studies only revealed minimal effects on fertility at plasma concentrations far in excess of human therapeutic concentrations (more than 500-fold).
The safety of rizatriptan for use in human pregnancy has not been established. Animal studies do not indicate harmful effects at dose levels that exceed therapeutic dose levels with respect to the development of the embryo or foetus, or the course of gestation, parturition and post-natal development.
Because animal reproductive and developmental studies are not always predictive of human response, MAXALT should be used during pregnancy only if clearly needed.
Studies in rats indicated very high milk transfer of rizatriptan occurred. Transient, very slight decreases in pre-weaning pup body weights were observed only when the mother’s systemic exposure was well in excess of the maximum exposure level for humans. No data exist in humans.
Therefore, caution should be exercised when administering rizatriptan to women who are breast-feeding. Infant exposure should be minimised by avoiding breast-feeding for 24 hours after treatment.
Migraine or treatment with MAXALT may cause somnolence in some patients. Dizziness has also been reported in some patients receiving MAXALT. Patients should, therefore, evaluate their ability to perform complex tasks during migraine attacks and after administration of MAXALT.
MAXALT (as the tablet and oral lyophilisate formulation) was evaluated in 8630 adult patients for up to one year in controlled clinical studies. The most common side effects evaluated in clinical studies were dizziness, somnolence, and asthenia/fatigue.
The following side effects have been evaluated in clinical studies and/or reported in post-marketing experience: (Very common [≥1/10]; Common [≥1/100, <1/10]; Uncommon [≥1/1000, <1/100]; Rare [≥1/10,000 <1/1,000]; Very rare [<1/10000], not known [cannot be estimated from the available data]).
Rare: hypersensitivity reaction, anaphylaxis/anaphylactoid reaction.
Common: insomnia
Uncommon: disorientation, nervousness.
Common: dizziness, somnolence, paraesthesia, headache, hypoaesthesia, decreased mental acuity.
Uncommon: ataxia, vertigo, dysgeusia/bad taste, tremor, syncope.
Not known: seizure, serotonin syndrome.
Uncommon: blurred vision.
Common: palpitation.
Uncommon: arrhythmia, ECG abnormalities, tachycardia
Rare: cerebrovascular accident (most of these adverse reactions have been reported in patients with risk factors predictive of coronary artery disease), bradycardia
Not known: myocardial ischaemia or infarction (most of these adverse reactions have been reported in patients with risk factors predictive of coronary artery disease).
Uncommon: hypertension, hot flushes/flashes.
Not known: peripheral vascular ischaemia.
Common: pharyngeal discomfort.
Uncommon: dyspnoea.
Rare: wheezing.
Common: nausea, dry mouth, vomiting, diarrhoea, dyspepsia.
Uncommon: thirst.
Not known: ischemic colitis.
Common: flushing.
Uncommon: pruritus, urticaria, angioedema (e.g. facial oedema, tongue swelling, pharyngeal oedema) (for angioedema see also section 4.4), rash, sweating.
Not known: toxic epidermal necrolysis.
Common: regional heaviness, neck pain, stiffness.
Uncommon: regional tightness, muscle weakness, facial pain, myalgia.
Common: asthenia/fatigue, pain in abdomen or chest.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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