1. Administration Route - Oral
CONTRAINDICATIONS
Sumatriptan succinate tablets should not be given to patients with history, symptoms, or signs of
ischemic cardiac, cerebrovascular, or peripheral vascular syndromes. In addition, patients with other
significant underlying cardiovascular diseases should not receive sumatriptan succinate tablets.
Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable
angina of effort and vasospastic forms of angina such as the Prinzmetal variant), all forms of
myocardial infarction, and silent myocardial ischemia. Cerebrovascular syndromes include, but are
not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease
includes, but is not limited to, ischemic bowel disease (see WARNINGS).
Because sumatriptan succinate tablets may increase blood pressure, they should not be given to
patients with uncontrolled hypertension.
Concurrent administration of MAO-A inhibitors or use within 2 weeks of discontinuation of
MAO-A inhibitor therapy is contraindicated (see CLINICAL PHARMACOLOGY, Drug
Interactions and DRUG INTERACTIONS).
Sumatriptan succinate tablets should not be administered to patients with hemiplegic or basilar
migraine.
Sumatriptan succinate tablets and any ergotamine-containing or ergot-type medication (like
dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should
sumatriptan succinate and another 5-HT1 agonist.
Sumatriptan succinate tablets are contraindicated in patients with hypersensitivity to sumatriptan or
any of their components.
Sumatriptan succinate tablets are contraindicated in patients with severe hepatic impairment.
WARNINGS
Sumatriptan succinate tablets should only be used where a clear diagnosis of migraine headache has
been established.
Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac
Events: Sumatriptan should not be given to patients with documented ischemic or vasospastic
coronary artery disease (CAD) (see CONTRAINDICATIONS). It is strongly recommended that
sumatriptan not be given to patients in whom unrecognized CAD is predicted by the presence of
risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family
history of CAD, female with surgical or physiological menopause, or male over 40 years of age)
unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is
reasonably free of coronary artery and ischemic myocardial disease or other significant underlying
cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular
disease or predisposition to coronary artery vasospasm is modest, at best. If, during the
cardiovascular evaluation, the patient's medical history or electrocardiographic investigations reveal
findings indicative of, or consistent with, coronary artery vasospasm or myocardial ischemia,
sumatriptan should not be administered (see CONTRAINDICATIONS).
For patients with risk factors predictive of CAD, who are determined to have a satisfactory
cardiovascular evaluation, it is strongly recommended that administration of the first dose of
sumatriptan take place in the setting of a physician's office or similar medically staffed and equipped
facility unless the patient has previously received sumatriptan. Because cardiac ischemia can occur
in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion
of use an electrocardiogram (ECG) during the interval immediately following sumatriptan succinate
tablets, in these patients with risk factors.
It is recommended that patients who are intermittent long-term users of sumatriptan and who have
or acquire risk factors predictive of CAD, as described above, undergo periodic interval
cardiovascular evaluation as they continue to use sumatriptan.
The systematic approach described above is intended to reduce the likelihood that patients with
unrecognized cardiovascular disease will be inadvertently exposed to sumatriptan.
Drug-Associated Cardiac Events and Fatalities: Serious adverse cardiac events, including acute
myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported
within a few hours following the administration of sumatriptan succinate injection or sumatriptan
succinate tablets. Considering the extent of use of sumatriptan in patients with migraine, the
incidence of these events is extremely low.
The fact that sumatriptan can cause coronary vasospasm, that some of these events have occurred
in patients with no prior cardiac disease history and with documented absence of CAD, and the
close proximity of the events to sumatriptan use support the conclusion that some of these cases
were caused by the drug. In many cases, however, where there has been known underlying
coronary artery disease, the relationship is uncertain.
Premarketing Experience with Sumatriptan: Of 6348 patients with migraine who participated in
premarketing controlled and uncontrolled clinical trials of oral sumatriptan, two experienced clinical
adverse events shortly after receiving oral sumatriptan that may have reflected coronary
vasospasm. Neither of these adverse events was associated with a serious clinical outcome.
Among the more than 1900 patients with migraine who participated in premarketing controlled
clinical trials of subcutaneous sumatriptan, there were 8 patients who sustained clinical events
during or shortly after receiving sumatriptan that may have reflected coronary artery vasospasm.
Six of these 8 patients had ECG changes consistent with transient ischemia, but without
accompanying clinical symptoms or signs. Of these 8 patients, 4 had either findings suggestive of
CAD or risk factors predictive of CAD prior to study enrollment.
Among approximately 4000 patients with migraine who participated in premarketing controlled and
uncontrolled clinical trials of sumatriptan nasal spray, one patient experienced an asymptomatic
subendocardial infarction possibly subsequent to a coronary vasospastic event.
Postmarketing Experience with Sumatriptan: Serious cardiovascular events, some resulting in
death, have been reported in association with the use of sumatriptan succinate injection or tablets.
The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine
definitively the proportion of the reported cases that were actually caused by sumatriptan or to
reliably assess causation in individual cases. On clinical grounds, the longer the latency between the
administration of sumatriptan succinate and the onset of the clinical event, the less likely the
association is to be causative. Accordingly, interest has focused on events beginning within 1 hour
of the administration of sumatriptan succinate.
Cardiac events that have been observed to have onset within 1 hour of sumatriptan administration
include: coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular
tachycardia and ventricular fibrillation, cardiac arrest, and death.
Some of these events occurred in patients who had no findings of CAD and appear to represent
consequences of coronary artery vasospasm. However, among domestic reports of serious cardiac
events within 1 hour of sumatriptan administration, almost all of the patients had risk factors
predictive of CAD and the presence of significant underlying CAD was established in most cases
(see CONTRAINDICATIONS).
Drug-Associated Cerebrovascular Events and Fatalities: Cerebral hemorrhage, subarachnoid
hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with
oral or subcutaneous sumatriptan, and some have resulted in fatalities. The relationship of
sumatriptan to these events is uncertain. In a number of cases, it appears possible that the
cerebrovascular events were primary, sumatriptan 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, care should be taken to
exclude other potentially serious neurological conditions. It should also be noted that patients with
migraine may be at increased risk of certain cerebrovascular events (e.g., cerebrovascular
accident, transient ischemic attack).
Other Vasospasm-Related Events: Sumatriptan may cause vasospastic reactions other than
coronary artery vasospasm. Both peripheral vascular ischemia and colonic ischemia with abdominal
pain and bloody diarrhea have been reported.
Increase in Blood Pressure: Significant elevation in blood pressure, including hypertensive crisis,
has been reported on rare occasions in patients with and without a history of hypertension.
Sumatriptan is contraindicated in patients with uncontrolled hypertension (see
CONTRAINDICATIONS). Sumatriptan should be administered with caution to patients with
controlled hypertension as transient increases in blood pressure and peripheral vascular resistance
have been observed in a small proportion of patients.
Concomitant Drug Use: In patients taking MAO-A inhibitors, sumatriptan plasma levels attained
after treatment with recommended doses are sevenfold higher following oral administration than
those obtained under other conditions. Accordingly, the coadministration of sumatriptan succinate
tablets and an MAO-A inhibitor is contraindicated (see CLINICAL PHARMACOLOGY and
CONTRAINDICATIONS).
Hypersensitivity: Hypersensitivity (anaphylaxis/anaphylactoid) reactions have occurred on rare
occasions in patients receiving sumatriptan. Such reactions can be life threatening or fatal. In
general, hypersensitivity reactions to drugs are more likely to occur in individuals with a history of
sensitivity to multiple allergens (see CONTRAINDICATIONS).
PRECAUTIONS
General
Chest discomfort and jaw or neck tightness have been reported following use of sumatriptan
succinate tablets and have also been reported infrequently following administration of sumatriptan
nasal spray. Chest, jaw, or neck tightness is relatively common after administration of sumatriptan
succinate injection. Only rarely have these symptoms been associated with ischemic ECG changes.
However, because sumatriptan may cause coronary artery vasospasm, patients who experience
signs or symptoms suggestive of angina following sumatriptan should be evaluated for the presence
of CAD or a predisposition to Prinzmetal's variant angina before receiving additional doses of
sumatriptan, and should be monitored electrocardiographically if dosing is resumed and similar
symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of
decreased arterial flow, such as ischemic bowel syndrome or Raynaud's syndrome following
sumatriptan should be evaluated for atherosclerosis or predisposition to vasospasm (see
WARNINGS).
Sumatriptan succinate should also be administered with caution to patients with diseases that may
alter the absorption, metabolism, or excretion of drugs, such as impaired hepatic or renal function.
There have been rare reports of seizure following administration of sumatriptan. Sumatriptan should
be used with caution in patients with a history of epilepsy or structural brain lesions that lower their
seizure threshold.
Care should be taken to exclude other potentially serious neurologic conditions before treating
headache in patients not previously diagnosed with migraine headache or who experience a
headache that is atypical for them. There have been rare reports where patients received
sumatriptan for severe headaches that were subsequently shown to have been secondary to an
evolving neurologic lesion (see WARNINGS).
For a given attack, if a patient does not respond to the first dose of sumatriptan, the diagnosis of
migraine should be reconsidered before administration of a second dose.
Binding to Melanin-Containing Tissues: In rats treated with a single subcutaneous dose (0.5
mg/kg) or oral dose (2 mg/kg) of radiolabeled sumatriptan, the elimination half-life of radioactivity
from the eye was 15 and 23 days, respectively, suggesting that sumatriptan and/or its metabolites
bind to the melanin of the eye. Because there could be accumulation in melanin-rich tissues over
time, this raises the possibility that sumatriptan could cause toxicity in these tissues after extended
use. However, no effects on the retina related to treatment with sumatriptan were noted in any of
the oral or subcutaneous toxicity studies. Although no systematic monitoring of ophthalmologic
function was undertaken in clinical trials, and no specific recommendations for ophthalmologic
monitoring are offered, prescribers should be aware of the possibility of long-term ophthalmologic
effects.
Corneal Opacities: Sumatriptan causes corneal opacities and defects in the corneal epithelium in
dogs; this raises the possibility that these changes may occur in humans. While patients were not
systematically evaluated for these changes in clinical trials, and no specific recommendations for
monitoring are being offered, prescribers should be aware of the possibility of these changes (See
ANIMAL PHARMACOLOGY).
Information for the Patient
See PATIENT PACKAGE INSERT at the end of the Intranasal product information for additional
information for patients.
Laboratory Tests
No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment
with sumatriptan.
Drug/Laboratory Test Interactions
Sumatriptan succinate tablets are not known to interfere with commonly employed clinical
laboratory tests.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Carcinogenesis: In carcinogenicity studies, rats and mice were given sumatriptan by oral gavage
(rats: 104 weeks), or drinking water (mice: 78 weeks). Average exposures achieved in mice
receiving the highest dose (target dose of 160 mg/kg per day) were approximately 40 times the
exposure attained in humans after the maximum recommended single oral dose of 100 mg. The
highest dose administered to rats (160 mg/kg per day, reduced from 360 mg/kg per day during week
21) was approximately 15 times the maximum recommended single human dose of 100 mg on a
mg/m2 basis. There was no evidence of an increase in tumors in either species related to
sumatriptan administration.
Mutagenesis: 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). In two cytogenetics assays (the in vitro human lymphocyte assay
and the in vivo rat micronucleus assay) sumatriptan was not associated with clastogenic activity.
Impairment of Fertility: In a study in which male and female rats were dosed daily with oral
sumatriptan 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 50 and 500 mg/kg per day. The
highest no-effect dose for this finding was 5 mg/kg a day, or approximately one-half of the
maximum recommended single human oral dose of 100 mg on a mg/m2 basis. It is not clear
whether the problem is associated with treatment of the males or females or both combined. In a
similar study by the subcutaneous route there was no evidence of impaired fertility at 60 mg/kg per
day, the maximum dose tested, which is equivalent to approximately 6 times the maximum
recommended single human oral dose of 100 mg on a mg/m2 basis.
Pregnancy Category C
In reproductive toxicity studies in rats and rabbits, oral treatment with sumatriptan was associated
with embroylethality, fetal abnormalities, and pup mortality. When administered by the intravenous
route to rabbits, sumatriptan has been shown to be embryolethal. There are no adequate and
well-controlled studies in pregnant women. Therefore, sumatriptan succinate tablets should be used
during pregnancy only if the potential benefit justifies the potential risk to the fetus. In assessing this
information, the following findings should be considered.
Embryolethality: When given orally or intravenously to pregnant rabbits daily throughout the period
of organogenesis, sumatriptan caused embryolethality at doses at or close to those producing
maternal toxicity. In the oral studies this dose was 100 mg/kg per day and in the intravenous studies
this dose was 2.0 mg/kg per day. The mechanism of the embryolethality is not known. The highest
no-effect dose for embryolethality by the oral route was 50 mg/kg per day, which is approximately 9
times the maximum single recommended human oral dose of 100 mg on a mg/m2 basis. By the
intravenous route, the highest no-effect dose was 0.75 mg/kg per day, or approximately one-tenth of
the maximum single recommended human oral dose of 100 mg on a mg/m2 basis.
The intravenous administration of sumatriptan to pregnant rats throughout organogenesis at 12.5
mg/kg per day, the maximum dose tested, did not cause embryolethality. This dose is equivalent to
the maximum single recommended human oral dose of 100 mg on a mg/m2 basis. Additionally, in a
study in rats given subcutaneous sumatriptan daily, prior to and throughout pregnancy at 60 mg/kg
per day, the maximum dose tested, there was no evidence of increased embryo/fetal lethality. This
dose is equivalent to approximately 6 times the maximum recommended single human oral dose of
100 mg on a mg/m2 basis.
Teratogenicity: Oral treatment of pregnant rats with sumatriptan during the period of
organogenesis resulted in an increased incidence of blood vessel abnormalities (cervicothoracic and
umbilical) at doses of approximately 250 mg/kg per day or higher. The highest no-effect dose was
approximately 60 mg/kg per day, which is approximately 6 times the maximum single recommended
human oral dose of 100 mg on a mg/m2 basis. Oral treatment of pregnant rabbits with sumatriptan
during the period of organogenesis resulted in an increased incidence of cervicothoracic vascular
and skeletal abnormalities. The highest no-effect dose for these effects was 15 mg/kg per day, or
approximately 3 times the maximum single recommended human oral dose of 100 mg on a mg/m2
basis.
A study in which rats were dosed daily with oral sumatriptan prior to and throughout gestation
demonstrated embryo/fetal toxicity (decreased body weight, decreased ossification, increased
incidence of rib variations) and an increased incidence of a syndrome of malformations (short
tail/short body and vertebral disorganization) at 500 mg/kg per day. The highest no-effect dose was
50 mg/kg per day, or approximately 5 times the maximum single recommended human oral dose of
100 mg on a mg/m2 basis. In a study in rats dosed daily with subcutaneous sumatriptan prior to and
throughout pregnancy, at a dose of 60 mg/kg per day, the maximum dose tested, there was no
evidence of teratogenicity. This dose is equivalent to approximately 6 times the maximum
recommended single human oral dose of 100 mg on a mg/m2 basis.
Pup Deaths: Oral treatment of pregnant rats with sumatriptan during the period of organogenesis
resulted in a decrease in pup survival between birth and postnatal day 4 at doses of approximately
250 mg/kg per day or higher. The highest no-effect dose for this effect was approximately 60
mg/kg per day, or 6 times the maximum single recommended human oral dose of 100 mg on a
mg/m2 basis.
Oral treatment of pregnant rats with sumatriptan from gestational day 17 through postnatal day 21
demonstrated a decrease in pup survival measured at postnatal days 2, 4, and 20 at the dose of 1000
mg/kg per day. The highest no-effect dose for this finding was 100 mg/kg per day, approximately 10
times the maximum single recommended human oral dose of 100 mg on a mg/m2 basis. In a similar
study in rats by the subcutaneous route there was no increase in pup death at 81 mg/kg per day, the
highest dose tested, which is equivalent to 8 times the maximum single recommended human oral
dose of 100 mg/m2 basis.
To monitor fetal outcomes of pregnant women exposed to sumatriptan succinate, Glaxo Wellcome
Inc. maintains a Sumatriptan Pregnancy Registry. Physicians are encouraged to register patients by
calling (800) 336–2176.
Nursing Mothers
Sumatriptan is excreted in human breast milk. Therefore, caution should be exercised when
considering the administration of sumatriptan succinate tablets to a nursing woman.
Pediatric Use
Safety and effectiveness of sumatriptan succinate tablets in pediatric patients have not been
established.
Completed placebo-controlled clinical trials evaluating oral sumatriptan (25 to 100 mg) in pediatric
patients aged 12 to 17 years have 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. Postmarketing experience includes a limited number of reports that describe pediatric
patients who have experienced adverse events, some clinically serious, after use of subcutaneous
sumatriptan and/or oral sumatriptan. These reports include events similar in nature to those reported
rarely in adults. A myocardial infarct 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 events in pediatric patients who might receive
injectable, oral, or intranasal sumatriptan are not presently available, the use of sumatriptan in
patients aged younger than 18 years is not recommended.
Geriatric Use
The use of sumatriptan in elderly patients is not recommended because elderly patients are more
likely to have decreased hepatic function, they are at higher risk for CAD, and blood pressure
increases may be more pronounced in the elderly (see WARNINGS).
2. Administration Route – subcutaneous
CONTRAINDICATIONS
Sumatriptan succinate injection should not be given intravenously because of its potential to cause
coronary vasospas.
Because sumatriptan succinate injection may increase blood pressure, it should not be given to
patients with uncontrolled hypertension.
Sumatriptan succinate injection and any ergotamine-containing or ergot-type medication (like
dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should
sumatriptan succinate and another 5–HT1 agonist.
Sumatriptan succinate injection should not be administered to patients with hemiplegic or basilar
migraine.
Sumatriptan succinate injection is contraindicated in patients with hypersensitivity to sumatriptan or
any of its components.
Sumatriptan succinate injection is contraindicated in patients with patients with severe hepatic
impairment.
WARNINGS
Sumatriptan succinate injection should only be used where a clear diagnosis migraine or cluster
headache has been established. The prescriber should be aware that cluster headache patients
often possess one or more predictive risk factors for coronary artery disease (CAD).
Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac
Events: Sumatriptan should not be given to patients with documented ischemic or vasospastic CAD
(see CONTRAINDICATIONS). It is strongly recommended that sumatriptan not be given to
patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk
factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of
CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a
cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free
of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular
disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or
predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular
evaluation, the patient's medical history or electrocardiographic investigations reveal findings
indicative of or consistent with coronary artery vasospasm or myocardial ischemia, sumatriptan
should not be administered (see CONTRAINDICATIONS).
For patients with risk factors predictive of CAD who are determined to have a satisfactory
cardiovascular evaluation, it is strongly recommended that administration of the first dose of
sumatriptan injection take place in the setting of a physician's office or similar medically staffed and
equipped facility. Because cardiac ischemia can occur in the absence of clinical symptoms,
consideration should be given to obtaining on the first occasion of use an electrocardiogram (ECG)
during the interval immediately following sumatriptan succinate injection, in these patients with risk
factors.
It is recommended that patients who are intermittent long-term users of sumatriptan and who have
or acquire risk factors predictive of CAD, as described above, undergo periodic interval
cardiovascular evaluation as they continue to use sumatriptan. In considering this recommendation
for periodic cardiovascular evaluation, it is noted that patients with cluster headache are
predominantly male and over 40 years of age, which are risk factors for CAD.
The systematic approach described above is intended to reduce the likelihood that patients with
unrecognized cardiovascular disease will be inadvertently exposed to sumatriptan.
Drug-Associated Cardiac Events and Fatalities: See WARNINGS, Drug-Associated Cardiac
Events and Fatalities in the oral product information.
Premarketing Experience with Sumatriptan: See WARNINGS, Premarketing Experience with
Sumatriptan in the oral product information.
Postmarketing Experience: See WARNINGS, Postmarketing Experience in the oral product
information.
Drug-Associated Cerebrovascular Events and Fatalities: See WARNINGS, Drug-Associated
Cerebrovascular Events and Fatalities in the oral product information.
Other Vasospasm-Related Events: See WARNINGS, Other Vasospasm-Related Events in the
oral product information.
Increase in Blood Pressure: See WARNINGS, Increase in Blood Pressure in the oral product
information.
Concomitant Drug Use: In patients taking MAO-A inhibitors, sumatriptan plasma levels attained
after treatment with recommended doses are nearly double those obtained under other conditions.
Accordingly, the coadministration of sumatriptan and an MAO-A inhibitor is not generally
recommended. If such therapy is clinically warranted, however, suitable dose adjustment and
appropriate observation of the patient is advised (see CLINICAL PHARMACOLOGY).
Use in Women of Childbearing Potential: See PRECAUTIONS.
Hypersensitivity: See WARNINGS, Hypersensitivity in the oral product information.
PRECAUTIONS
General
Chest, jaw, or neck tightness is relatively common after administration of sumatriptan succinate
injection. Chest discomfort and jaw or neck tightness has been reported following use of
sumatriptan succinate tablets and has also been reported infrequently following the administration of
sumatriptan nasal spray. Only rarely have these symptoms been associated with ischemic ECG
changes. However, because sumatriptan may cause coronary artery vasospasm, patients who
experience signs or symptoms suggestive of angina following sumatriptan should be evaluated for
the presence of CAD or a predisposition to Prinzmetal variant angina before receiving additional
doses of sumatriptan and should be monitored electrocardiographically if dosing is resumed and
similar symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of
decreased arterial flow, such as ischemic bowel syndrome or Raynaud syndrome, following
sumatriptan should be evaluated for atherosclerosis or predisposition to vasospasm (see
WARNINGS).
Sumatriptan succinate injection should also be administered with caution to patients with diseases
that may alter the absorption, metabolism, or excretion of drugs, such as impaired hepatic or renal
function.
There have been rare reports of seizure following administration of sumatriptan. Sumatriptan should
be used with caution in patients with a history of epilepsy or structural brain lesions that lower their
seizure threshold.
Care should be taken to exclude other potentially serious neurologic conditions before treating
headache in patients not previously diagnosed with migraine or cluster headache or who experience
a headache that is atypical for them. There have been rare reports where patients received
sumatriptan for severe headaches that were subsequently shown to have been secondary to an
evolving neurologic lesion (see WARNINGS). For a given attack, if a patient does not respond to
the first dose of sumatriptan, the diagnosis of migraine or cluster headache should be reconsidered
before administration of a second dose.
Binding to Melanin-Containing Tissues
Because sumatriptan binds to melanin, it could accumulate in melanin-rich tissues (such as the eye)
over time. This raises the possibility that sumatriptan could cause toxicity in these tissues after
extended use. However, no effects on the retina related to treatment with sumatriptan were noted
in any of the toxicity studies. Although no systematic monitoring of ophthalmologic function was
undertaken in clinical trials, and no specific recommendations for ophthalmologic function was
undertaken in clinical trials, and no specific recommendations for ophthalmologic monitoring are
offered, prescribers should be aware of the possibility of long-term ophthalmologic effects (see
CLINICAL PHARMACOLOGY).
Corneal Opacities
Sumatriptan causes corneal opacities and defects in the corneal epithelium in dogs; this raises the
possibility that these changes may occur in humans. While patients were not systematically
evaluated for these changes in clinical trials, and no specific recommendations for monitoring are
being offered, prescribers should be aware of the possibility of these changes (see CLINICAL
PHARMACOLOGY).
Patients who are advised to self-administer sumatriptan succinate injection in medically
unsupervised situations should receive instruction on the proper use of the product from
the physician or other suitably qualified health care professional prior to doing so for the
first time.
Information for the Patient
With the autoinjector, the needle penetrates approximately ¼ of an inch (5 to 6 mm). Since the
injection is intended to be given subcutaneously, intramuscular or intravascular delivery should be
avoided. Patients should be directed to use injection sites with an adequate skin and subcutaneous
thickness to accommodate the length of the needle. See PATIENT PACKAGE INSERT at the
end of the Intranasal product information for additional information for patients.
Laboratory Tests
No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment
with sumatriptan.
Drug/Laboratory Test Interactions
Sumatriptan succinate is not known to interfere with commonly employed clinical laboratory tests.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
In carcinogenicity studies, rats and mice were given sumatriptan by oral gavage (rats: 104 weeks),
or drinking water (mice: 78 weeks). Average exposures achieved in mice receiving the highest dose
were approximately 110 times the exposure attained in humans after the maximum recommended
single dose of 6 mg. The highest dose to rats was approximately 260 times the maximum single
dose of 6 mg on a mg/m2 basis. 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). In two cytogenetics assays (the in vitro human lymphocyte assay and the in
vivo rat micronucleus assay) sumatriptan was not associated with clastogenic activity.
A fertility study (Segment I) by the subcutaneous route, during which male and female rats were
dosed daily with sumatriptan prior to and throughout the mating period, has shown no evidence of
impaired fertility at doses equivalent to approximately 100 times the maximum recommended single
human dose of 6 mg on a mg/m2 basis. 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 per day. The no-effect dose for this finding was approximately eight times the maximum
recommended single human dose of 6 mg on a mg/m2 basis. It is not clear whether the problem is
associated with the treatment of males or females or both.
Pregnancy Category C
Sumatriptan has been shown to be embryolethal in rabbits when given daily at a dose approximately
equivalent to the maximum recommended single human subcutaneous dose of 6 mg on a mg/m2
basis. There is no evidence that establishes that sumatriptan is a human teratogen; however, there
are no adequate and well-controlled studies in pregnant women. Sumatriptan succinate injection
should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In assessing this information, the following additional findings should be considered.
Embryolethality: When given intravenously to pregnant rabbits daily throughout the period of
organogenesis, sumatriptan caused embryolethality at doses at or close to those producing maternal
toxicity. The mechanism of the embryolethality is not known. These doses were approximately
equivalent to the maximum single human dose of 6 mg on a mg/m2 basis.
The intravenous administration of sumatriptan to pregnant rats throughout organogenesis at doses
that are approximately 20 times a human dose of 6 mg on a mg/m2 basis, did not cause
embryolethality. Additionally, in a study of pregnant rats given subcutaneous sumatriptan daily prior
to and throughout pregnancy, there was no evidence of increase embryo/fetal lethality.
Teratogenicity: Term fetuses from Dutch Stride rabbits treated during organogenesis with oral
sumatriptan exhibited an increased incidence of cervicothoracic vascular and skeletal abnormalities.
The functional significance of these abnormalities is not known. The highest no-effect dose for
these effects was 15 mg/kg per day, approximately 50 times the maximum single dose of 6 mg on a
mg/m2 basis.
In a study in rats dosed daily with subcutaneous sumatriptan prior to and throughout pregnancy,
there was no evidence of teratogenicity.
To monitor fetal outcomes of pregnant women exposed to sumatriptan succinate, Glaxo Wellcome
Inc. maintains a Sumatriptan Pregnancy Registry. Physicians are encouraged to register patients by
calling (800) 336–2176.
Nursing Mothers
Sumatriptan is excreted in human breast milk. Therefore, caution should be exercised when
considering the administration of any form of sumatriptan succinate to a nursing woman.
Pediatric Use
See PRECAUTIONS, Pediatric Use in the oral product information.
Geriatric Use
The use of sumatriptan in elderly patients is not recommended because elderly patients are more
likely to have decreased hepatic function, they are at higher risk for CAD, and blood pressure
increases may be more pronounced in the elderly (see WARNINGS).