Included as part of the PRECAUTIONS section.
Myocardial Ischemia, Myocardial Infarction, And
Zolmitriptan tablets are contraindicated in patients with
ischemic or vasospastic coronary artery disease (CAD). There have been rare
reports of serious cardiac adverse reactions, including acute myocardial infarction,
occurring within a few hours following administration of zolmitriptan tablets.
Some of these reactions occurred in patients without known CAD. 5-HT1 agonists
including zolmitriptan tablets may cause coronary artery vasospasm
(Prinzmetal's Angina), even in patients without a history of CAD.
Perform a cardiovascular evaluation in triptan-naïve
patients who have multiple cardiovascular risk factors (e.g., increased age,
diabetes, hypertension, smoking, obesity, strong family history of CAD) prior
to receiving zolmitriptan tablets. Do not administer zolmitriptan tablets if
there is evidence of CAD or coronary artery vasospasm [see CONTRAINDICATIONS].
For patients with multiple cardiovascular risk factors who have a negative
cardiovascular evaluation, consider administering the first zolmitriptan tablets
dose in a medically-supervised setting and performing an electrocardiogram
(ECG) immediately following zolmitriptan tablets administration. For such
patients, consider periodic cardiovascular evaluation in intermittent long-term
users of zolmitriptan tablets.
Life-threatening disturbances of cardiac rhythm including
ventricular tachycardia and ventricular fibrillation leading to death have been
reported within a few hours following the administration of 5- HT1 agonists.
Discontinue zolmitriptan tablets if these disturbances occur. Zolmitriptan
tablets are contraindicated in patients with Wolff-Parkinson-White syndrome or
arrhythmias associated with other cardiac accessory conduction pathway
disorders [see CONTRAINDICATIONS].
Chest, Throat, Neck And Jaw Pain/Tightness/Pressure
As with other 5-HT1 agonists, sensations of tightness,
pain, and pressure in the chest, throat, neck, and jaw commonly occur after
treatment with zolmitriptan tablets and is usually non-cardiac in origin. However,
perform a cardiac evaluation if these patients are at high cardiac risk. 5-HT1
agonists including zolmitriptan tablets are contraindicated in patients with
CAD or Prinzmetal's variant angina [see CONTRAINDICATIONS].
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke
have occurred in patients treated with 5- HT1 agonists, and some have resulted
in fatalities. In a number of cases, it appears possible that the cerebrovascular
events were primary, the 5-HT1 agonist having been administered in the
incorrect belief that the symptoms experienced were a consequence of migraine,
when they were not.
As with other acute migraine therapies, before treating
headaches in patients not previously diagnosed as migraineurs, and in
migraineurs who present with symptoms atypical for migraine, exclude other potentially
serious neurological conditions. Zolmitriptan tablets are contraindicated in
patients with a history of stroke or transient ischemic attack [see
Other Vasospasm Reactions
5-HT1 agonists, including zolmitriptan tablets, may cause
non-coronary vasospastic reactions, such as peripheral vascular ischemia,
gastrointestinal vascular ischemia and infarction (presenting with abdominal
pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In
patients who experience symptoms or signs suggestive of a vasospastic reaction
following the use of any 5-HT1 agonist, rule out a vasospastic reaction before
receiving additional zolmitriptan tablets doses [see CONTRAINDICATIONS].
Reports of transient and permanent blindness and
significant partial vision loss have been reported with the use of 5-HT1
agonists. Since visual disorders may be part of a migraine attack, a causal
relationship between these events and the use of 5-HT agonists has not been
Medication Overuse Headache
Overuse of acute migraine drugs (e.g. ergotamine,
triptans, opioids, or a combination of drugs for 10 or more days per month) may
lead to exacerbation of headache (medication overuse headache). Medication overuse
headache may present as migraine-like daily headaches or as a marked increase
in frequency of migraine attacks. Detoxification of patients, including
withdrawal of the overused drugs, and treatment of withdrawal symptoms (which
often includes a transient worsening of headache) may be necessary.
Serotonin syndrome may occur with triptans, including
zolmitriptan tablets , particularly during coadministration with selective
serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors
(SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see DRUG
INTERACTIONS]. Serotonin syndrome symptoms may include mental status
changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g.,
tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g.,
hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea,
vomiting, diarrhea). The onset of symptoms usually rapidly occurs within
minutes to hours of receiving a new or a greater dose of a serotonergic
medication. Discontinue zolmitriptan tablets if serotonin syndrome is suspected
[see DRUG INTERACTIONS].
Increase In Blood Pressure
Significant elevations in systemic blood pressure have
been reported in patients treated with 5-HT1 agonists including patients
without a history of hypertension; very rarely, these increases in blood pressure
have been associated with serious adverse reactions. In healthy subjects
treated with 5 mg of zolmitriptan tablets, an increase of 1 and 5 mm Hg in the
systolic and diastolic blood pressure, respectively, was seen. In a study of
patients with moderate to severe liver impairment, 7 of 27 patients experienced
20 to 80 mm Hg elevations in systolic and/or diastolic blood pressure after a
dose of 10 mg of zolmitriptan tablets.
As with all triptans, blood pressure should be monitored
in zolmitriptan tablets-treated patients. Zolmitriptan tablets are
contraindicated in patients with uncontrolled hypertension [see CONTRAINDICATIONS].
Patient Counseling Information
See FDA Approved Patient Labeling (PATIENT INFORMATION).
Myocardial Ischemia and/or Infarction, Prinzmetal's
angina, Other Vasospastic Reactions, and Cerebrovascular Events
Inform patients that zolmitriptan tablets may cause
serious cardiovascular adverse reactions such as myocardial infarction or
stroke, which may result in hospitalization and even death. Although serious cardiovascular
reactions can occur without warning symptoms, instruct patients to be alert for
the signs and symptoms of chest pain, shortness of breath, weakness, slurring
of speech, and instruct them to ask for medical advice when observing any
indicative sign or symptoms. Instruct patients to seek medical advice if they
have symptoms of other vasospastic reactions [see WARNINGS AND PRECAUTIONS].
Medication Overuse Headache
Inform patients that use of drugs to treat acute
migraines for 10 or more days per month may lead to an exacerbation of
headache, and encourage patients to record headache frequency and drug use
(e.g., by keeping a headache diary) [see WARNINGS AND PRECAUTIONS].
Inform patients about the risk of serotonin syndrome with
the use of zolmitriptan tablets or other triptans, particularly during combined
use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine
reuptake inhibitors (SNRIs) [see WARNINGS AND PRECAUTIONS].
Inform patients that zolmitriptan tablets should not be
used during pregnancy unless the potential benefit justifies the potential risk
to the fetus [see Use in Specific Populations].
Advise patients to notify their healthcare provider if
they are breastfeeding or plan to breastfeed [see Use in Specific
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Zolmitriptan was administered to mice and rats at doses
up to 400 mg/kg/day. Mice were dosed for 85 weeks (males) and 92 weeks
(females); rats were dosed for 101 weeks (males) and 86 weeks (females). There
was no evidence of drug-induced tumors in mice at plasma exposures (AUC) up to
approximately 700 times that in humans at the maximum recommended human dose
(MRHD) of 10 mg/day. In rats, there was an increase in the incidence of thyroid
follicular cell hyperplasia and thyroid follicular cell adenomas in male rats
receiving 400 mg/kg/day. No increase in tumors was observed in rats at 100 mg/kg/day,
a dose associated with a plasma AUC approximately 700 times that in humans at
Zolmitriptan was positive in an in vitro bacterial
reverse mutation (Ames) assay and in an in vitro chromosomal aberration assay
in human lymphocytes. Zolmitriptan was negative in an in vitro mammalian gene
cell mutation (CHO/HGPRT) assay and in oral in vivo mouse micronucleus assays
in mouse and rat.
Impairment Of Fertility
Studies of male and female rats administered zolmitriptan
prior to and during mating and up to implantation showed no impairment of
fertility at oral doses up to 400 mg/kg/day. The plasma exposure (AUC) at this
dose was approximately 3000 times that in humans at the MRHD.
Use In Specific Populations
Pregnancy Category C: There are no adequate and
well-controlled studies in pregnant women; therefore, zolmitriptan tablets
should be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus. In reproductive toxicity studies in rats and rabbits, oral
administration of zolmitriptan to pregnant animals resulted in embryolethality
and fetal abnormalities (malformations and variations) at clinically relevant
When zolmitriptan was administered to pregnant rats
during the period of organogenesis at oral doses of 100, 400, and 1200
mg/kg/day (plasma exposures (AUCs) ≈280, 1100, and 5000 times the human
AUC at the maximum recommended human dose (MRHD) of 10 mg/day), there was a
dose-related increase in embryolethality. A no-effect dose for embryolethality
was not established. When zolmitriptan was administered to pregnant rabbits
during the period of organogenesis at oral doses of 3, 10, and 30 mg/kg/day
(plasma AUCs ≈1, 11, and 42 times the human AUC at the MRHD), there were
increases in embryolethality and in fetal malformations and variations. The
no-effect dose for adverse effects on embryo-fetal development was associated
with plasma AUC similar to that in humans at the MRHD. When female rats were
given zolmitriptan during gestation, parturition, and lactation at oral doses
of 25, 100, and 400 mg/kg/day (plasma AUCs ≈70, 280, and 1100 times that
in human at the MRHD), an increased incidence of hydronephrosis was found in
the offspring. The no-effect dose was associated with a plasma AUC ≈280
times that in humans at the MRHD.
It is not known whether zolmitriptan is excreted in human
milk. Because many drugs are excreted in human milk, and because of the
potential for serious adverse reactions in nursing infants from zolmitriptan
tablets, a decision should be made whether to discontinue nursing or to
discontinue the drug, taking into account the importance of the drug to the
In rats, oral dosing with zolmitriptan resulted in levels
in milk up to 4 times higher than in plasma.
The safety and effectiveness in pediatric patients have
not been established. Therefore, zolmitriptan tablets are not recommended for
use in patients under 18 years of age.
One randomized, placebo-controlled clinical trial of
zolmitriptan tablets (2.5, 5 and 10 mg) evaluated 696 pediatric patients (aged
12-17 years) with migraines. This study did not demonstrate the efficacy of zolmitriptan
tablets compared to placebo in the treatment of migraine in adolescents.
Adverse reactions in the adolescent patients treated with zolmitriptan tablets
were similar in nature and frequency to those reported in clinical trials in
adults treated with zolmitriptan tablets. Zolmitriptan tablets have not been studied
in pediatric patients less than 12 years old.
In the postmarketing experience with triptans, including
zolmitriptan tablets, there were no additional adverse reactions seen in
pediatric patients that were not seen in adults.
Clinical studies of zolmitriptan tablets did not include
sufficient numbers of subjects aged 65 and over to determine whether they
respond differently from younger subjects. Other reported clinical experience
has not identified differences in responses between the elderly and younger
patients. In general, dose selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.
A cardiovascular evaluation is recommended for geriatric
patients who have other cardiovascular risk factors (e.g., diabetes,
hypertension, smoking, obesity, strong family history of coronary artery
disease) prior to receiving zolmitriptan tablets [see WARNINGS AND
The pharmacokinetics of zolmitriptan were similar in
geriatric patients (aged > 65 years) compared to younger patients [see CLINICAL
Patients With Hepatic Impairment
After oral zolmitriptan tablets administration,
zolmitriptan blood levels were increased in patients with moderate to severe
hepatic impairment, and significant elevation in blood pressure was observed in
some of these patients [see WARNINGS AND PRECAUTIONS]. Therefore, adjust
the zolmitriptan tablets dose and administer with caution in patients with
moderate or severe hepatic impairment [see DOSAGE AND ADMINISTRATION and