Skip to Content


Active substance(s): RIZATRIPTAN BENZOATE

View full screen / Print PDF » Download PDF ⇩


Rizatriptan 10 mg orodispersible tablets


Each orodispersible tablet contains 14.530 mg of rizatriptan benzoate equivalent to 10
mg of rizatriptan.
For the full list of excipients, see section 6.1


Orodispersible tablet.
White to off-white coloured, circular, biconvex, uncoated tablets debossed with ‘F25’
on one side and plain on other side with a peppermint flavor




Therapeutic indications
Acute treatment of the headache phase of migraine attacks, with or without aura in


Posology and method of administration
Rizatriptan should not be used prophylactically.
Rizatriptan orodispersible tablets need not be taken with liquid.
The orodispersible tablet is packaged in an aluminium blister. Patients should
be instructed not to remove the orodispersible tablet from the blister until just
prior to dosing. The orodispersible tablet should then be removed from the

aluminium blister with dry hands and the placed on the tongue, where it will
dissolve and be swallowed with the saliva.
The orodispersible tablet can be used in situations in which liquids are not
available, or to avoid the nausea and vomiting that may accompany the
ingestion of tablets with liquids.
Adults 18 years of age and older
The recommended dose is 10 mg.
Redosing: Doses should be separated by at least 2 hours; no more than 2 doses
should be taken in any 24-hour period.

for headache recurrence within 24 hours: If headache returns after relief of
the initial attack, one further dose may be taken. The above dosing limits
should be observed.


after non-response: The effectiveness of a second dose for treatment of the
same attack, when an initial dose is ineffective, has not been examined in
controlled trials. Therefore, if a patient does not respond to the first dose, a
second dose should not be taken for the same attack.

Clinical studies have shown that patients who do not respond to treatment of
an attack are still likely to respond to treatment for subsequent attacks.
Some patients should receive the lower (5 mg) dose of Rizatriptan, in
particular the following patient groups:

patients on propranolol. Administration of rizatriptan should be separated
by at least 2 hours from administration of propranolol. (See section 4.5)


patients with mild or moderate renal insufficiency.


patients with mild to moderate hepatic insufficiency.

Doses should be separated by at least 2 hours; no more than 2 doses should be
taken in any 24-hour period.
Paediatric patients
Children and adolescents (under 18 years of age)
The safety and efficacy of rizatriptan in children and adolescents under 18
years of age has not yet been established.
Currently available data are described in section 5.1 and 5.2, but no
recommendation on a posology can be made.
Patients older than 65 years
The safety and effectiveness of rizatriptan in patients older than 65 years
have not been systematically evaluated.


Hypersensitivity to rizatriptan or to any of the excipients.
Concurrent administration of monoamine oxidase (MAO) inhibitors or use within two
weeks of discontinuation of MAO inhibitor therapy. (See section 4.5)
Rizatriptan is contra-indicated in patients with severe hepatic or severe renal
Rizatriptan is contra-indicated in patients with a previous cerebrovascular accident
(CVA) or transient ischemic attack (TIA).
Moderately severe or severe hypertension or untreated mild hypertension.
Established coronary artery disease, including ischemic heart disease (angina
pectoris, history of myocardial infarction, or documented silent ischemia), signs and
symptoms of ischemic 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).


Special warnings and precautions for use
Rizatriptan should only be administered to patients in whom a clear diagnosis of
migraine has been established. Rizatriptan should not be administered to patients with
basilar or hemiplegic migraine.
Rizatriptan 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 Rizatriptan.
(See section 4.3)
5-HT1B/1D receptor agonists have been associated with coronary vasospasm. In rare
cases, myocardial ischemia or infarction have been reported with 5-HT1B/1D receptor
agonists including Rizatriptan (see section 4.8)
Other 5-HT1B/1D agonists, (e.g. sumatriptan) should not be used concomitantly with
Rizatriptan. (See section 4.5).
It is advised to wait at least 6 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 (5HT1B/1D agonists) and herbal preparations containing St John's wort (Hypericum
Angioedema (e.g. facial edema, tongue swelling and pharyngeal edema) 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 potential for interaction should be considered when rizatriptan is administered to
patients taking CYP 2D6 substrates (see section 4.5)

Medication overuse headache (MOH)
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
Phenylketonurics: Phenylketonuric patients should be informed that phenylalanine
may be harmful. Rizatriptan orodispersible tablets contain aspartame (which contains


Interaction with other medicinal products and other forms of interaction
Ergotamine, ergot derivatives (including methysergide), other 5 HT 1B/1D receptor
agonists: Due to an additive effect, the concomitant use of rizatriptan and ergotamine,
ergot derivatives (including methysergide), or other 5 HT 1B/1D receptor agonists (e.g.
sumatriptan, zolmitriptan, naratriptan) increase the risk of coronary artery
vasoconstriction and hypertensive effects. This combination is contraindicated (see
section 4.3).
Monoamine oxidase inhibitors: Rizatriptan is principally metabolised via monoamine
oxidase, 'A' subtype (MAO-A). Plasma concentrations of rizatriptan and its active Nmonodesmethyl 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
Rizatriptan to patients taking inhibitors of MAO is contraindicated. (See section 4.3)
Beta-blockers: 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 Rizatriptan should be used. (See section 4.2)
In a drug-interaction study, nadolol and metoprolol did not alter plasma
concentrations of rizatriptan.
Selective Serotonin Reuptake Inhibitors (SSRIs) /Serotonin Norepinephrine Reuptake
Inhibitors (SNRIs) and Serotonin Syndrome: 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.


Pregnancy and lactation
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).
Use during pregnancy
The safety of rizatriptan for the 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, Rizatriptan should be used during pregnancy only if clearly needed.
Use during lactation
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.


Effects on ability to drive and use machines
Migraine or treatment with Rizatriptan may cause somnolence in some patients.
Dizziness has also been reported in some patients receiving Rizatriptan. Patients
should, therefore, evaluate their ability to perform complex tasks during migraine
attacks and after administration of Rizatriptan.


Undesirable effects
Rizatriptan (as the tablet and orodispersible tablet formulation) was evaluated in over
3,600 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]).

Immune system disorders:

hypersensitivity reaction


anaphylaxis/anaphylactoid reaction.

Psychiatric disorders:

disorientation, insomnia, nervousness.

Nervous system disorders:
dizziness, somnolence, paraesthesia, headache, hypoaesthesia,
decreased mental acuity, tremor.

ataxia, vertigo.


dysgeusia/bad taste, syncope, serotonin syndrome.

Not known:


Eye disorders:

blurred vision.

Cardiac disorders:

palpitation, tachycardia.

Rare: Myocardial ischaemia or infarction, cerebrovascular accident. Most of these
adverse reactions have been reported in patients with risk factors predictive of
coronary artery disease.
Not known:

arrhythmia, bradycardia

Vascular disorders:

hot flushes/flashes.



Not known:

peripheral vascular ischaemia.

Respiratory, thoracic and mediastinal disorders:

pharyngeal discomfort, dyspnoea.



Gastro-intestinal disorders:

nausea, dry mouth, vomiting, diarrhoea.


thirst, dyspepsia.

Not known:

ischemic colitis.

Skin and subcutaneous tissue disorders:

flushing, sweating, rash

pruritus, urticaria, angioedema (e.g. facial oedema, tongue swelling,
pharyngeal edema) (for angioedema see also section 4.4).

toxic epidermal necrolysis

Musculoskeletal and connective tissue disorders:

regional heaviness.


neck pain, regional tightness, stiffness, muscle weakness.


facial pain.

Not known:


General disorders and administration site conditions:

asthenia/fatigue, pain in abdomen or chest.

Not known:


ECG abnormalities.

Rizatriptan 40 mg (administered as either a single tablet dose or as two doses with a
2-hour interdose interval) was generally well tolerated in over 300 adult patients;
dizziness and somnolence were the most common drug-related adverse effects.
In a clinical pharmacology study in which 12 adult subjects received rizatriptan, at
total cumulative doses of 80 mg (given within four hours), two subjects experienced
syncope and/or bradycardia. One subject, a female aged 29 years, developed
vomiting, bradycardia, and dizziness beginning three hours after receiving a total of
80 mg rizatriptan (administered over two hours). A third-degree AV block,
responsive to atropine, was observed an hour after the onset of the other symptoms.
The second subject, a 25 year-old male, experienced transient dizziness, syncope,
incontinence, and a 5-second systolic pause (on ECG monitor) immediately after a
painful venipuncture. The venipuncture occurred two hours after the subject had
received a total of 80 mg rizatriptan (administered over four hours).

In addition, based on the pharmacology of rizatriptan, hypertension or other more
serious cardiovascular symptoms could occur after overdosage. Gastro-intestinal
decontamination, (e.g. gastric lavage followed by activated charcoal) should be
considered in patients suspected of an overdose with Rizatriptan. Clinical and
electrocardiographic monitoring should be continued for at least 12 hours, even if
clinical symptoms are not observed.
The effects of haemo- or peritoneal dialysis on serum concentrations of rizatriptan are




Pharmacodynamic properties
Mechanism of action : Selective serotonin (5HT1B/1D) agonists
Pharmacotherapeutic group: antimigraine preparations, selective serotonin (5HT1)
agonists, ATC-code: N02CC04
Rizatriptan binds selectively with high affinity to human 5-HT1B and 5-HT1D receptors
and has little or no effect or pharmacological activity at 5-HT2, 5 HT3; adrenergic
alpha1, alpha2 or beta; D1, D2, dopaminergic, histaminic H1; muscarinic; or
benzodiazepine receptors.
The therapeutic activity of rizatriptan in treating migraine headache may be attributed
to its agonist effects at 5-HT1B and 5-HT1D receptors on the extracerebral intracranial
blood vessels that are thought to become dilated during an attack and on the
trigeminal sensory nerves that innervate them. Activation of these 5-HT1B and 5HT1D receptors may result in constriction of pain-producing intracranial blood vessels
and inhibition of neuropeptide release that leads to decreased inflammation in
sensitive tissues and reduced central trigeminal pain signal transmission.
Pharmacodynamic effects
The efficacy of Rizatriptan orodispersible tablets in the acute treatment of migraine
attacks was established in two multicentre, randomised, placebo-controlled trials that
were similar in design to the trials of Rizatriptan Tablets. In one study (n=311), by 2
hours post-dosing, relief rates in patients treated with Rizatriptan orodispersible
tablets were approximately 66% for rizatriptan 5 mg and 10 mg, compared to 47% in
the placebo group. In a larger study (n=547), by 2 hours post-dosing, relief rates were
59% in patients treated with Rizatriptan orodispersible tablets 5 mg, and 74% after 10
mg, compared to 28% in the placebo group. Rizatriptan orodispersible tablets also
relieved the disability, nausea, photophobia, and phonophobia which accompanied the
migraine episodes. A significant effect on pain relief was observed as early as 30

minutes post-dosing in one of the two clinical trials for the 10 mg dose (see section
5.2 ).
Based on studies with the oral tablet, rizatriptan remains effective in treating
menstrual migraine, i.e. migraine that occurs within 3 days before or after the onset of
Adolescents (12-17 years of age)
The efficacy of rizatriptan orodispersible tablets in paediatric patients (12 to 17 years
of age) was evaluated in a multicenter, randomized, double-blind, placebo-controlled,
parallel group study (n=570). The patient population was required to be historically
non-responsive to NSAIDs and acetaminophen therapy. Patients with a qualifying
migraine headache initially administered placebo within 30 minutes of onset.
Following the 15 minute placebo run-in, subjects who did not respond to placebo then
treated a single migraine attack with placebo or rizatriptan. Using a weight-based
dosing strategy, patients 20 kg to <40 kg received 5mg rizatriptan and patients 40 kg
received 10mg rizatriptan.

In this enriched population study, a difference of 9% between active treatment and
placebo was observed for the primary efficacy endpoint of pain freedom (reduction
from moderate or severe pain to no pain) 2 hours after treatment (31% under
rizatriptan vs. 22% for placebo (p=0.025)). No significant difference for the
secondary endpoint of pain relief (reduction from moderate or severe pain to mild or
no pain) was found.
Children (6-11 years of age)
The efficacy of rizatriptan orodispersible tablets was also evaluated in paediatric
patients 6 to 11 years of age in the same acute placebo-controlled clinical trial
(n=200). The percentage of patients achieving pain freedom 2 hours after treatment
was not statistically significantly different in patients who received rizatriptan
orodispersible tablets 5 and 10 mg, compared with those who received placebo
(39.8% vs. 30.4%, p=0.269).
Rizatriptan orodispersible tablets enables migraine patients to treat their migraine
attacks without having to swallow liquids. This may allow patients to administer their
medication earlier, for example, when liquids are not available, and to avoid possible
worsening of GI symptoms by swallowing liquids.


Pharmacokinetic properties
Rizatriptan is rapidly and completely absorbed following oral administration.
The mean oral bioavailability of the orodispersible tablet is approximately 40-45%,
and mean peak plasma concentrations (Cmax) are reached in approximately 1.58 hours
(Tmax). The time to maximum plasma concentration following administration of
rizatriptan as the orodispersible formulation is delayed by 30 – 60 minutes relative to
the tablet.

Effect of food: The effect of food on the absorption of rizatriptan from the
orodispersible tablet has not been studied. For the rizatriptan tablets, Tmax is delayed
by approximately 1 hour when the tablets are administered in the fed state. A further
delay in the absorption of rizatriptan may occur when the orodispersible tablet is
administered after meals.
Rizatriptan is minimally bound (14%) to plasma proteins. The volume of distribution
is approximately 140 litres in male subjects, and 110 litres in female subjects.
The primary route of rizatriptan metabolism is via oxidative deamination by
monoamine oxidase-A (MAO-A) to the indole acetic acid metabolite, which is not
pharmacologically active. N monodesmethyl-rizatriptan, a metabolite with activity
similar to that of parent compound at the 5-HT1B/1D receptors, is formed to a minor
degree, but does not contribute significantly to the pharmacodynamic activity of
rizatriptan. Plasma concentrations of N-monodesmethyl-rizatriptan are approximately
14% of those of parent compound, and it is eliminated at a similar rate. Other minor
metabolites include the N-oxide, the 6-hydroxy compound, and the sulfate conjugate
of the 6-hydroxy metabolite. None of these minor metabolites is pharmacologically
active. Following oral administration of 14C-labelled rizatriptan, rizatriptan accounts
for about 17% of circulating plasma radioactivity.
Following intravenous administration, AUC in men increases proportionally and in
women near-proportionally with the dose over a dose range of 10-60 µg/kg.
Following oral administration, AUC increases near-proportionally with the dose over
a dose range of 2.5-10 mg. The plasma half-life of rizatriptan in males and females
averages 2-3 hours. The plasma clearance of rizatriptan averages about 1,000-1,500
ml/min in males and about 900-1,100 ml/min in females; about 20-30% of this is
renal clearance. Following an oral dose of 14C-labelled rizatriptan, about 80% of the
radioactivity is excreted in urine, and about 10% of the dose is excreted in faeces.
This shows that the metabolites are excreted primarily via the kidneys.
Consistent with its first pass metabolism, approximately 14% of an oral dose is
excreted in urine as unchanged rizatriptan while 51% is excreted as indole acetic acid
metabolite. No more than 1% is excreted in urine as the active N monodesmethyl
If rizatriptan is administered according to the maximum dosage regimen, no drug
accumulation in the plasma occurs from day to day.
Characteristics in patients
The following data are based on studies with the oral tablet formulation.

Patients with a migraine attack: A migraine attack does not affect the
pharmacokinetics of rizatriptan.
Gender: The AUC of rizatriptan (10 mg orally) was about 25% lower in males as
compared to females, Cmax was 11% lower, and Tmax occurred at approximately the
same time. This apparent pharmacokinetic difference was of no clinical significance.
Elderly: The plasma concentrations of rizatriptan observed in elderly subjects (age
range 65 to 77 years) after tablet administration were similar to those observed in
young adults.
Paediatric: A pharmacokinetics study of rizatriptan (as the orodispersible
formulation) was conducted in paediatric migraineurs 6 to 17 years of age. The mean
exposures following a single dose administration of 5 mg rizatriptan orodispersible
tablet to paediatric patients weighing 20-39 kg or 10 mg rizatriptan orodispersible
tablet to paediatric patients weighing 40 kg were respectively 15% lower and 17%
higher compared to the exposure observed following single dose administration of 10
mg rizatriptan orodispersible tablet to adults. The clinical relevance of these
differences is unclear.

Hepatic impairment (Child-Pugh's score 5-6): Following oral tablet administration in
patients with hepatic impairment caused by mild alcoholic cirrhosis of the liver,
plasma concentrations of rizatriptan were similar to those seen in young male and
female subjects. A significant increase in AUC (50%) and Cmax (25%) was observed
in patients with moderate hepatic impairment (Child Pugh's score 7).
Pharmacokinetics were not studied in patients with Child Pugh's score >7 (severe
hepatic impairment).
Renal impairment: In patients with renal impairment (creatinine clearance 10 60
ml/min/1.73 m2), the AUC of rizatriptan after tablet administration was not
significantly different from that in healthy subjects. In haemodialysis patients
(creatinine clearance <10 ml/min/1.73 m2), the AUC for rizatriptan was
approximately 44% greater than that in patients with normal renal function. The
maximal plasma concentration of rizatriptan in patients with all degrees of renal
impairment was similar to that in healthy subjects.


Preclinical safety data
Preclinical data indicate no risk for humans based on conventional studies of repeat
dose toxicity, genotoxicity, carcinogenic potential, reproductive and developmental
toxicity, safety pharmacology, and pharmacokinetics and metabolism




List of excipients

Cellulose Microcrystalline [E460]
Starch Pregelatinized
Mannitol [E421]
Crospovidone (Type A) [E1202]
Aspartame [E951]
Peppermint Flavor (Maltodextrin, Natural Flavors, Modified Corn Starch)
Sodium Stearyl Fumarate [E485]


Not applicable


Shelf life
2 years


Special precautions for storage
This medicinal product does not require any special storage conditions


Nature and contents of container
Rizatriptan orodispersible tablets are available in Polyamide/ Aluminium / PVC Aluminium foil blister packs of: 2, 3, 6, 10, 12 and 18 tablets.
Not all pack sizes may be marketed


Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local


Milpharm Limited
Ares Block

Odyssey Business Park
West End Road
Ruislip HA4 6QD
United Kingdom


PL 16363/0321





Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.