Included as part of the PRECAUTIONS section.
Myocardial Ischemia, Myocardial Infarction, And
The use of IMITREX injection is contraindicated in patients
with ischemic or vasospastic CAD. There have been rare reports of serious
cardiac adverse reactions, including acute myocardial infarction, occurring
within a few hours following administration of IMITREX injection. Some of these
reactions occurred in patients without known CAD. IMITREX injection may cause
coronary artery vasospasm (Prinzmetal's angina), even in patients without a
history of CAD.
Perform a cardiovascular evaluation in triptan-naive
patients who have multiple cardiovascular risk factors (e.g., increased age,
diabetes, hypertension, smoking, obesity, strong family history of CAD) prior
to receiving IMITREX injection. If there is evidence of CAD or coronary artery
vasospasm, IMITREX injection is contraindicated. For patients with multiple
cardiovascular risk factors who have a negative cardiovascular evaluation,
consider administering the first dose of IMITREX injection in a medically
supervised setting and performing an electrocardiogram (ECG) immediately
following administration of IMITREX injection. For such patients, consider
periodic cardiovascular evaluation in intermittent long-term users of IMITREX
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 IMITREX injection if these disturbances occur.
IMITREX injection is contraindicated in patients with Wolff-Parkinson-White
syndrome or arrhythmias associated with other cardiac accessory conduction
Chest, Throat, Neck, And/Or Jaw Pain/Tightness/Pressure
Sensations of tightness, pain, pressure, and heaviness in
the precordium, throat, neck, and jaw commonly occur after treatment with
IMITREX injection and are usually non-cardiac in origin. However, perform a
cardiac evaluation if these patients are at high cardiac risk. The use of
IMITREX injection is contraindicated in patients with CAD and those with
Prinzmetal's variant angina.
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. Also, patients with migraine may be at increased
risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA).
Discontinue IMITREX injection if a cerebrovascular event occurs.
Before treating headaches in patients not previously
diagnosed with migraine or cluster headache or in patients who present with
atypical symptoms, exclude other potentially serious neurological conditions.
IMITREX injection is contraindicated in patients with a history of stroke or
Other Vasospasm Reactions
IMITREX injection 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 non-coronary vasospasm reaction following the use of any
5-HT1 agonist, rule out a vasospastic reaction before receiving additional
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-HT1 agonists has not been
Medication Overuse Headache
Overuse of acute migraine drugs (e.g., ergotamine,
triptans, opioids, or combination of these 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
Serotonin syndrome may occur with IMITREX injection, 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 occurs within minutes to hours of receiving a new or a
greater dose of a serotonergic medication. Discontinue IMITREX injection if
serotonin syndrome is suspected.
Increase In Blood Pressure
Significant elevation in blood pressure, including
hypertensive crisis with acute impairment of organ systems, has been reported
on rare occasions in patients treated with 5-HT1 agonists, including patients
without a history of hypertension. Monitor blood pressure in patients treated
with IMITREX. IMITREX injection is contraindicated in patients with
Anaphylactic/anaphylactoid reactions have occurred in
patients receiving IMITREX. Such reactions can be life-threatening or fatal. In
general, anaphylactic reactions to drugs are more likely to occur in
individuals with a history of sensitivity to multiple allergens. IMITREX
injection is contraindicated in patients with a history of hypersensitivity
reaction to IMITREX.
Seizures have been reported following administration of
IMITREX. Some have occurred in patients with either a history of seizures or
concurrent conditions predisposing to seizures. There are also reports in
patients where no such predisposing factors are apparent. IMITREX injection
should be used with caution in patients with a history of epilepsy or
conditions associated with a lowered seizure threshold.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (PATIENT INFORMATION and Instructions for Use).
Risk Of Myocardial Ischemia And/Or Infarction,
Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, And
Inform patients that IMITREX injection may cause serious
cardiovascular side effects such as myocardial infarction or stroke. Although
serious cardiovascular events can occur without warning symptoms, patients
should be alert for the signs and symptoms of chest pain, shortness of breath,
irregular heartbeat, significant rise in blood pressure, weakness, and slurring
of speech, and should ask for medical advice if any indicative sign or symptoms
are observed. Apprise patients of the importance of this follow-up [see WARNINGS
Inform patients that anaphylactic/anaphylactoid reactions
have occurred in patients receiving IMITREX injection. Such reactions can be
life-threatening or fatal. In general, anaphylactic reactions to drugs are more
likely to occur in individuals with a history of sensitivity to multiple allergens
[see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS].
Concomitant Use With Other Triptans Or Ergot Medications
Inform patients that use of IMITREX injection within 24
hours of another triptan or an ergot-type medication (including dihydroergotamine
or methysergide) is contraindicated [see CONTRAINDICATIONS, DRUG
Caution patients about the risk of serotonin syndrome
with the use of IMITREX injection or other triptans, particularly during combined
use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see WARNINGS AND
PRECAUTIONS, DRUG INTERACTIONS].
Medication Overuse Headache
Inform patients that use of acute migraine drugs 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].
Advise patients to notify their healthcare provider if
they become pregnant during treatment or plan to become pregnant [see Use In
Advise patients to notify their healthcare provider if
they are breastfeeding or plan to breastfeed [see Use In Specific
Ability To Perform Complex Tasks
Treatment with IMITREX injection may cause somnolence and
dizziness; instruct patients to evaluate their ability to perform complex tasks
after administration of IMITREX injection.
How To Use IMITREX Injection
Instruct patients to read the Instructions for Use before
starting therapy. Provide patients instruction on the proper use of IMITREX
injection if they are able to self-administer IMITREX injection in medically
unsupervised situations. Instruct patients on storage and disposal of the pen
[see HOW SUPPLIED/Storage and Handling].
Inform patients that the needle in the IMITREX STATdose
Pen penetrates approximately 1/4 of an inch (5 to 6 mm). Inform patients that
the injection is intended to be given subcutaneously and intramuscular or
intravascular delivery should be avoided. Instruct patients to use injection
sites with an adequate skin and subcutaneous thickness to accommodate the
length of the needle.
Trademarks are owned by or licensed to the GSK group of
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In carcinogenicity studies in mouse and rat, sumatriptan
was administered orally for 78 weeks and 104 weeks, respectively, at doses up
to 160 mg/kg/day (the high dose in rat was reduced from 360 mg/kg/day during
Week 21). The highest dose to mice and rats was approximately 130 and 260 times
the single MRHD of 6 mg administered subcutaneously on a mg/m² basis. There was
no evidence in either species of an increase in tumors related to sumatriptan
Sumatriptan was negative in in vitro (bacterial reverse
mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal
aberration in human lymphocytes) and in vivo (rat micronucleus) assays.
Impairment Of Fertility
When sumatriptan (5, 50, 500 mg/kg/day) was administered
orally to male and female rats prior to and throughout the mating period, there
was a treatment-related decrease in fertility secondary to a decrease in mating
in animals treated with doses greater than 5 mg/kg/day. It is not clear whether
this finding was due to an effect on males or females or both.
When sumatriptan was administered by subcutaneous
injection to male and female rats prior to and throughout the mating period,
there was no evidence of impaired fertility at doses up to 60 mg/kg/day.
Use In Specific Populations
Data from a prospective pregnancy exposure registry and
epidemiological studies of pregnant women have not detected an increased
frequency of birth defects or a consistent pattern of birth defects among women
exposed to sumatriptan compared with the general population (see Data).
In developmental toxicity studies in rats and rabbits, oral administration of
sumatriptan to pregnant animals was associated with embryolethality, fetal
abnormalities, and pup mortality. When administered by the intravenous route to
pregnant rabbits, sumatriptan was embryolethal (see Data).
In the U.S. general population, the estimated background
risk of major birth defects and of miscarriage in clinically recognized
pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of
major birth defects among deliveries to women with migraine ranged from 2.2% to
2.9% and the reported rate of miscarriage was 17%, which were similar to rates
reported in women without migraine.
Disease-Associated Maternal and/or Embryo/Fetal Risk:
Several studies have suggested that women with migraine may be at increased
risk of preeclampsia during pregnancy.
The Sumatriptan/Naratriptan/Treximet (sumatriptan and
naproxen sodium) Pregnancy Registry, a population-based international
prospective study, collected data for sumatriptan from January 1996 to
September 2012. The Registry documented outcomes of 626 infants and fetuses
exposed to sumatriptan during pregnancy (528 with earliest exposure during the first
trimester, 78 during the second trimester, 16 during the third trimester, and 4
unknown). The occurrence of major birth defects (excluding fetal deaths and
induced abortions without reported defects and all spontaneous pregnancy
losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95%
CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95%
CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at
least a 1.73-to 1.91-fold increase in the rate of major malformations. The
number of exposed pregnancy outcomes accumulated during the registry was
insufficient to support definitive conclusions about overall malformation risk
or for making comparisons of the frequencies of specific birth defects. Of the
20 infants with reported birth defects after exposure to sumatriptan in the
first trimester, 4 infants had ventricular septal defects, including one infant
who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric
stenosis. No other birth defect was reported for more than 2 infants in this
In a study using data from the Swedish Medical Birth
Register, live births to women who reported using triptans or ergots during
pregnancy were compared with those of women who did not. Of the 2,257 births
with first-trimester exposure to sumatriptan, 107 infants were born with
malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked
data from the Medical Birth Registry of Norway to the Norwegian Prescription
Database compared pregnancy outcomes in women who redeemed prescriptions for
triptans during pregnancy, as well as a migraine disease comparison group who
redeemed prescriptions for sumatriptan before pregnancy only, compared with a
population control group. Of the 415 women who redeemed prescriptions for
sumatriptan during the first trimester, 15 had infants with major congenital
malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who
redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20
had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to
2.88]), each compared with the population comparison group. Additional smaller
observational studies evaluating use of sumatriptan during pregnancy have not
suggested an increased risk of teratogenicity.
Oral administration of sumatriptan to pregnant rats
during the period of organogenesis resulted in an increased incidence of fetal
blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect
dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral
administration of sumatriptan to pregnant rabbits during the period of
organogenesis resulted in increased incidences of embryolethality and fetal
cervicothoracic vascular and skeletal abnormalities. Intravenous administration
of sumatriptan to pregnant rabbits during the period of organogenesis resulted
in an increased incidence of embryolethality. The highest oral and intravenous
no-effect doses for developmental toxicity in rabbits were 15 and 0.75
Oral administration of sumatriptan to rats prior to and
throughout gestation resulted in embryofetal toxicity (decreased body weight,
decreased ossification, increased incidence of skeletal abnormalities). The
highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated
orally with sumatriptan during organogenesis, there was a decrease in pup
survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral
treatment of pregnant rats with sumatriptan during the latter part of gestation
and throughout lactation resulted in a decrease in pup survival. The highest
no-effect dose for this finding was 100 mg/kg/day.
Sumatriptan is excreted in human milk following
subcutaneous administration (see Data). There are no data on the effects
of sumatriptan on the breastfed infant or the effects of sumatriptan on milk
The developmental and health benefits of breastfeeding
should be considered along with the mother's clinical need for IMITREX
injection and any potential adverse effects on the breastfed infant from
sumatriptan or from the underlying maternal condition.
Infant exposure to sumatriptan can be minimized by
avoiding breastfeeding for 12 hours after treatment with IMITREX injection.
Following subcutaneous administration of a 6 mg dose of
IMITREX injection in 5 lactating volunteers, sumatriptan was present in milk.
Safety and effectiveness in pediatric patients have not
been established. IMITREX injection is not recommended for use in patients
younger than 18 years of age.
Two controlled clinical trials evaluated IMITREX nasal
spray (5 to 20 mg) in 1,248 pediatric migraineurs aged 12 to 17 years who treated
a single attack. The trials did not establish the efficacy of IMITREX nasal
spray compared with placebo in the treatment of migraine in pediatric patients.
Adverse reactions observed in these clinical trials were similar in nature to
those reported in clinical trials in adults.
Five controlled clinical trials (2 single-attack trials,
3 multiple-attack trials) evaluating oral IMITREX (25 to 100 mg) in pediatric
patients aged 12 to 17 years enrolled a total of 701 pediatric migraineurs.
These trials did not establish the efficacy of oral IMITREX compared with
placebo in the treatment of migraine in pediatric patients. Adverse reactions
observed in these clinical trials were similar in nature to those reported in
clinical trials in adults. The frequency of all adverse reactions in these
patients appeared to be both dose-and age-dependent, with younger patients
reporting reactions more commonly than older pediatric patients.
Postmarketing experience documents that serious adverse reactions
have occurred in the pediatric population after use of subcutaneous, oral,
and/or intranasal IMITREX. These reports include reactions similar in nature to
those reported rarely in adults, including stroke, visual loss, and death. A
myocardial infarction has been reported in a 14-year-old male following the use
of oral IMITREX; clinical signs occurred within 1 day of drug administration.
Clinical data to determine the frequency of serious adverse reactions in
pediatric patients who might receive subcutaneous, oral, or intranasal IMITREX
are not presently available.
Clinical trials of IMITREX injection did not include
sufficient numbers of patients aged 65 years and older to determine whether
they respond differently from younger patients. 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 CAD) prior to receiving IMITREX
injection [see WARNINGS AND PRECAUTIONS].