Included as part of the PRECAUTIONS section.
Myocardial Ischemia, Myocardial Infarction, And Prinzmetal's
The use of ZEMBRACE SymTouch 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 sumatriptan injection.
Some of these reactions occurred in patients without known CAD. 5-HT1 agonists,
including ZEMBRACE SymTouch 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 ZEMBRACE SymTouch injection. If there is evidence of CAD or
coronary artery vasospasm, ZEMBRACE SymTouch injection is contraindicated. For
patients with multiple cardiovascular risk factors who have a negative
cardiovascular evaluation, consider administering the first dose of ZEMBRACE SymTouch
injection in a medically supervised setting and performing an electrocardiogram
(ECG) immediately following ZEMBRACE SymTouch injection. For such patients,
consider periodic cardiovascular evaluation in intermittent long-term users of
ZEMBRACE SymTouch injection.
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 ZEMBRACE SymTouch injection if these disturbances
occur. ZEMBRACE SymTouch 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
sumatriptan injection and are usually non-cardiac in origin. However, perform a
cardiac evaluation if these patients are at high cardiac risk. The use of
ZEMBRACE SymTouch injection is contraindicated in patients shown to have 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 ZEMBRACE SymTouch injection if a cerebrovascular event occurs.
Before treating headaches in patients not previously
diagnosed with migraine or in patients who present with atypical symptoms,
exclude other potentially serious neurological conditions. ZEMBRACE SymTouch
injection is contraindicated in patients with a history of stroke or TIA.
Other Vasospasm Reactions
ZEMBRACE SymTouch 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 ZEMBRACE SymTouch injections.
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 have not been
Medication Overuse Headache
Overuse of acute migraine drugs (e.g., ergotamine,
triptans, opioids, 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 ZEMBRACE SymTouch
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 ZEMBRACE SymTouch injection if serotonin syndrome is
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 ZEMBRACE SymTouch. ZEMBRACE SymTouch injection is contraindicated in
patients with uncontrolled hypertension.
Anaphylactic reactions have occurred in patients
receiving sumatriptan. 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. ZEMBRACE
SymTouch injection is contraindicated in patients with a history of
hypersensitivity reaction to sumatriptan.
Seizures have been reported following administration of
sumatriptan. 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. ZEMBRACE SymTouch
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 ZEMBRACE
SymTouch 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 when observing any indicative sign or symptoms are observed.
Apprise patients of the importance of this follow-up [see WARNINGS
Inform patients that
anaphylactic reactions have occurred in patients receiving sumatriptan
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 and WARNINGS
Concomitant Use With Other
Triptans Or Ergot Medications
Inform patients that use of
ZEMBRACE SymTouch injection within 24 hours of another triptan or an ergot-type
medication (including dihydroergotamine or methylsergide) is contraindicated [see
CONTRAINDICATIONS, DRUG INTERACTIONS].
Caution patients about the risk
of serotonin syndrome with the use of ZEMBRACE SymTouch injection or other
triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO
inhibitors [see WARNINGS AND PRECAUTIONS,
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].
Inform patients that ZEMBRACE
SymTouch injection should not be used during pregnancy unless the potential
benefit justifies the potential risk to the fetus [see Use in Specific
Advise patients to notify their
healthcare provider if they are breastfeeding or plan to breastfeed [see Use
in Specific Populations].
Ability To Perform Complex
Treatment with ZEMBRACE
SymTouch injection may cause somnolence and dizziness; instruct patients to
evaluate their ability to perform complex tasks during migraine attacks and
after administration of ZEMBRACE SymTouch injection.
How To Use ZEMBRACE SymTouch
Provide patients instruction on
the proper use of ZEMBRACE SymTouch injection if they are able to
self-administer ZEMBRACE SymTouch injection in medically unsupervised
Inform patients that the needle
in the ZEMBRACE SymTouch penetrates approximately ¼ of an inch (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.
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 highest dose in rat was reduced
from 360 mg/kg/day during Week 21). There was no evidence in either species of
an increase in tumors related to sumatriptan administration.
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
Impairment Of Fertility
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
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.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled trials of
sumatriptan injection in pregnant women. 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. ZEMBRACE SymTouch injection should be used during pregnancy only
if the potential benefit justifies the potential risk to the fetus.
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. Infant exposure to sumatriptan can be minimized by
avoiding breastfeeding for 12 hours after treatment with ZEMBRACE SymTouch
Safety and effectiveness in pediatric patients have not
been established. ZEMBRACE SymTouch injection is not recommended for use in
patients younger than 18 years of age.
Two controlled clinical trials evaluated sumatriptan
nasal spray (5 to 20 mg) in 1,248 pediatric migraineurs 12 to 17 years of age
who treated a single attack. The trials did not establish the efficacy of
sumatriptan 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 sumatriptan (25 to 100 mg) in
pediatric subjects 12 to 17 years of age enrolled a total of 701 pediatric
migraineurs. These trials did not establish the efficacy of oral sumatriptan
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
Postmarketing experience documents that serious adverse
reactions have occurred in the pediatric population after use of subcutaneous,
oral, and/or intranasal sumatriptan. 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 sumatriptan; 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 SUMATRIPTAN are not presently available.
Clinical trials of sumatriptan injection did not include
sufficient numbers of subjects aged 65 and over to determine whether they
respond differently from younger patients. Other reported clinical experience
has not identified differences in responses between the elderly and younger
subjects. 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 ZEMBRACE SymTouch injection [see WARNINGS AND PRECAUTIONS].