Included as part of the PRECAUTIONS section.
Risk Of Injury During Magnetic Resonance Imaging (MRI)
ZECUITY contains metal parts and must be removed before
an MRI procedure.
Allergic Contact Dermatitis
Use of ZECUITY may lead to allergic contact dermatitis
(ACD). In two long-term open-label studies where patients were allowed to treat
multiple migraine attacks for up to 1 year, the overall adverse event rate of
ACD was 4%. ZECUITY should be discontinued if ACD is suspected. Erythema is commonly
seen with use of ZECUITY and is not by itself an indication of sensitization.
Following sensitization with ZECUITY, erythematous plaque and/or
erythemato-vesicular or erythemato-bullous eruptions may develop. Clinical
course is characterized by crescendo phenomenon of worsening pruritus and
appearance over time with slower resolution to normal of affected skin areas.
Patients sensitized from use of ZECUITY, as evidenced by
development of ACD, may develop systemic sensitization or other systemic
reactions if sumatriptan-containing products are taken via other routes, e.g.,
orally or subcutaneously. It is possible that some patients who developed ACD
with sumatriptan by exposure to ZECUITY, and who have developed systemic
sensitization, may not be able to take sumatriptan in any form.
Patients who develop ACD with ZECUITY and require
treatment with sumatriptan via other routes should receive their first
subsequent dose under close medical supervision.
Myocardial Ischemia, Myocardial Infarction, And Prinzmetal’s
The use of ZECUITY 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. Some of these reactions
occurred in patients without known CAD. 5-HT1 agonists, including
ZECUITY, 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 using ZECUITY. Do not use ZECUITY 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 using the first ZECUITY TDS in a medically supervised setting and
performing an electrocardiogram (ECG) upon activation of ZECUITY. For such
patients, consider periodic cardiovascular evaluation in intermittent long-term
users of ZECUITY.
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
5HT1 agonists. Discontinue ZECUITY if these disturbances occur.
ZECUITY is contraindicated in patients with Wolff-Parkinson-White syndrome or
arrhythmias associated with other cardiac accessory conduction pathway
disorders [see CONTRAINDICATIONS].
Chest, Throat, Neck And/Or Jaw Pain/Tightness /Pressure
Sensations of tightness, pain, pressure, and heaviness in
the chest, throat, neck, and jaw commonly occur after treatment with
sumatriptan and are usually non-cardiac in origin. However, perform a cardiac evaluation
if these patients are at high cardiac risk. The use of ZECUITY is
contraindicated in patients shown with CAD and those with Prinzmetal's variant
angina [see CONTRAINDICATIONS].
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke
have occurred in patients treated with 5HT1 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 atypical symptoms, exclude other potentially serious
neurological conditions. ZECUITY is contraindicated in patients with a history
of stroke or TIA [see CONTRAINDICATIONS].
Other Vasospasm Reactions
5-HT1 agonists, including ZECUITY, 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 using ZECUITY [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-HT1 agonists have
not been clearly established.
Medication Overuse Headache
Overuse of acute migraine drugs (e.g., ergotamine,
triptans, opioids, 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
ZECUITY, 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
ZECUITY 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 ZECUITY. ZECUITY is contraindicated in patients with uncontrolled
hypertension [see CONTRAINDICATIONS].
Anaphylactic/anaphylactoid 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. ZECUITY is contraindicated
in patients with prior serious anaphylactic reaction.
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. ZECUITY should be
used with caution in patients with a history of epilepsy or conditions
associated with a lowered seizure threshold.
Electrically-Active Implantable Or Body-Worn Medical
ZECUITY should not be applied in areas near or over
electrically-active implantable or body-worn medical devices (e.g., implantable
cardiac pacemaker, body-worn insulin pump, implantable deep brain stimulator).
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION
and Instructions for Use).
How To Use ZECUITY
Advise patients to carefully read the Patient
Instructions for Use. Only patients who are able to understand and follow the
instructions should use ZECUITY.
Advise patients that the ZECUITY iontophoretic
transdermal system (TDS) must be properly applied and activated within 15
minutes of initiating Step 1 (Pull Tabs) of the Patient Instructions for Use,
or the TDS will not operate.
Advise patients not to bathe, shower or swim while
Advise patients that upon removal of the ZECUITY TDS,
most patients experience some skin redness under the transdermal system, which
usually disappears within 24 hours.
Advise patients that ZECUITY is single-use and should not
be cut. Advise patients that no more than two ZECUITY TDS should be used in a
24 hour period, and that a second ZECUITY TDS should not be applied until at
least 2 hours after activation of the first ZECUITY TDS [see DOSAGE AND
Instruct patients to apply the ZECUITY TDS to the upper
arm or thigh and not to other areas of the body. Instruct patients to apply the
ZECUITY TDS to dry intact, non-irritated skin on a site that is relatively hair
free and without scars, tattoos, abrasions, or other skin conditions (i.e.,
generalized skin irritation or disease including eczema, psoriasis, melanoma,
Advise patients that the ZECUITY TDS should not be
applied to a previous application site until the site remains erythema free for
3 days [see DOSAGE AND ADMINISTRATION].
Inform patients that the safety of using more than 4
ZECUITY in one month has not been established.
Risk Of Injury During Magnetic Resonance Imaging (MRI) Procedure
Inform patients that ZECUITY contains metal parts and
must be removed before an MRI procedure.
Potential For Allergic Contact Dermatitis
Caution patients about the potential for developing
allergic contact dermatitis (ACD) after use of ZECUITY. Inform patients of the
signs and symptoms of ACD, and instruct patients to seek medical advice if they
develop skin lesions suggestive of ACD. Inform patients that it is possible
that some patients who develop ACD with sumatriptan by exposure to ZECUITY may
not be able to take sumatriptan in any form.
Risk Of Myocardial Ischemia And/Or Infarction,
Prinzmetal’s Angina, Other Vasospasm-related Events, Arrhythmias, And Cerebrovascular
Inform patients that the medication in ZECUITY or other
triptans may cause serious cardiovascular side effects such as myocardial
infarction or stroke, which may result in hospitalization and even death. Although
serious cardiovascular events can occur without warning symptoms, advise
patients that they should be alert for the signs and symptoms of chest pain,
shortness of breath, weakness, slurring of speech, and should seek medical
advice when observing any indicative sign or symptoms. Apprise patients of the
importance of this follow-up [see WARNINGS AND PRECAUTIONS].
Inform patients that anaphylactic/anaphylactoid 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 [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 ZECUITY 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 physician if they are
breast-feeding or plan to breast-feed [see Use In Specific Populations].
Ability To Perform Complex Tasks
Since migraines or treatment with sumatriptan may cause
somnolence and dizziness, instruct patients to evaluate their ability to
perform complex tasks during migraine attacks and after using ZECUITY.
Caution patients about the risk of serotonin syndrome
with the use of ZECUITY or other triptans, particularly during combined use
with SSRIs, SNRIs, TCAs, and MAO inhibitors [see WARNINGS AND PRECAUTIONS
and DRUG INTERACTIONS].
ZECUITY® is a registered trademark of Teva
Pharmaceuticals International GmbH. The other brands listed are trademarks of
their respective owners and are not trademarks of Teva Pharmaceuticals International
GmbH. The makers of these brands are not affiliated with and do not endorse
Teva Pharmaceuticals International GmbH or its affiliates or products.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In carcinogenicity studies, rats and mice were given
sumatriptan by oral gavage. Mice were dosed for 78 weeks and rats were dosed
for 104 weeks. There was no evidence of an increase in tumors in either species
related to sumatriptan administration.
Sumatriptan was not mutagenic in the presence or absence
of metabolic activation when tested in two gene mutation assays (the Ames test
and the in vitro mammalian Chinese hamster V79/HGPRT assay). It was not
clastogenic in two cytogenetics assays (in vitro human lymphocyte assay and in
vivo rat micronucleus assay).
Impairment Of Fertility
A fertility study by the subcutaneous route, during which
male and female rats were dosed daily with sumatriptan prior to and throughout
the mating period, demonstrated no evidence of impaired fertility. However,
following oral administration, a treatment-related decrease in fertility, secondary
to a decrease in mating, was seen for rats treated with 50 and 500 mg/kg/day.
It is not clear whether the problem is associated with the treatment of males
or females or both.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies in
pregnant women. ZECUITY should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
When sumatriptan was administered intravenously to
pregnant rabbits daily throughout the period of organogenesis, embryolethality
was observed at doses at or close to those producing maternal toxicity. Oral
administration of sumatriptan to rabbits during organogenesis was associated
with increased incidences of fetal vascular and skeletal abnormalities; the
highest no-effect dose for these effects was 15 mg/kg/day. The intravenous
administration of sumatriptan to pregnant rats throughout organogenesis did not
produce evidence of embryolethality. The subcutaneous administration of
sumatriptan to pregnant rats prior to and throughout pregnancy did not produce
evidence of embryolethality or teratogenicity.
It is not known whether sumatriptan is excreted in human
milk following transdermal administration. Because many drugs are excreted in
human milk, and because of the potential for serious adverse reactions in
nursing infants from ZECUITY, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the importance of the
drug to the mother.
Safety and effectiveness in pediatric patients have not been
Two controlled clinical trials evaluated sumatriptan
nasal spray (5 to 20 mg) in 1,248 adolescent migraineurs aged 12 to 17 years
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 adolescents.
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 studies,
3 multiple-attack studies) evaluating oral sumatriptan (25 to 100 mg) in
pediatric patients aged 12 to 17 years enrolled a total of 701 adolescent migraineurs.
These studies did not establish the efficacy of oral sumatriptan compared to
placebo in the treatment of migraine in adolescents. Adverse events observed in
these clinical trials were similar in nature to those reported in clinical
trials in adults. The frequency of all adverse events in these patients appeared
to be both dose- and age dependent, with younger patients reporting events more
commonly than older adolescents.
Post-marketing experience documents that serious adverse
events have occurred in the pediatric population after use of subcutaneous,
oral, and/or intranasal sumatriptan. These reports include events 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. Since 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, the use of ZECUITY in
patients under 18 years of age is not recommended.
Clinical trials of ZECUITY 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 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 using ZECUITY
[see WARNINGS AND PRECAUTIONS].