imitrex
Generic Name: (
sumatriptan succinate)
Dosage Type: injection Organization: GlaxoSmithKline
DESCRIPTION
IMITREX (sumatriptan
succinate) Injection is a selective 5-hydroxytryptamine1 receptor
subtype agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide
succinate (1:1), and it has the following structure:
The
empirical formula is C14H21N3O2S•C4H6O4,
representing a molecular weight of 413.5.
Sumatriptan
succinate is a white to off-white powder that is readily soluble in water
and in saline.
IMITREX Injection is a clear, colorless
to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection.
Each 0.5 mL of IMITREX Injection 8 mg/mL solution contains 4 mg
of sumatriptan (base) as the succinate salt and 3.8 mg of sodium chloride,
USP in Water for Injection, USP. Each 0.5 mL of IMITREX Injection 12 mg/mL
solution contains 6 mg of sumatriptan (base) as the succinate salt and
3.5 mg of sodium chloride, USP in Water for Injection, USP. The pH range
of both solutions is approximately 4.2 to 5.3. The osmolality of both injections
is 291 mOsmol.
CLINICAL PHARMACOLOGY
Mechanism of Action
Sumatriptan has been
demonstrated to be a selective agonist for a vascular 5-hydroxytryptamine1 receptor
subtype (probably a member of the 5-HT1D family) with no significantaffinity (as measured using standard radioligand binding assays) or pharmacological
activity at 5-HT2, 5-HT3 receptor subtypes or at alpha1-,
alpha2-, or beta-adrenergic; dopamine1; dopamine2;
muscarinic; or benzodiazepine receptors.
The vascular
5-HT1 receptor subtype to which sumatriptan binds selectively,
and through which it presumably exerts its antimigrainous effect, has been
shown to be present on cranial arteries in both dog and primate, on the human
basilar artery, and in the vasculature of the isolated dura mater of humans.
In these tissues, sumatriptan activates this receptor to cause vasoconstriction,
an action in humans correlating with the relief of migraine and cluster headache.
In the anesthetized dog, sumatriptan selectively reduces the carotid arterial
blood flow with little or no effect on arterial blood pressure or total peripheral
resistance. In the cat, sumatriptan selectively constricts the carotid arteriovenous
anastomoses while having little effect on blood flow or resistance in cerebral
or extracerebral tissues.
Corneal Opacities
Dogs receiving oral sumatriptan developed corneal opacities
and defects in the corneal epithelium. Corneal opacities were seen at the
lowest dosage tested, 2 mg/kg/day, and were present after 1 month
of treatment. Defects in the corneal epithelium were noted in a 60-week study.
Earlier examinations for these toxicities were not conducted and no-effect
doses were not established; however, the relative exposure at the lowest dose
tested was approximately 5 times the human exposure after a 100-mg oral dose
or 3 times the human exposure after a 6-mg subcutaneous dose.
Melanin Binding
In rats with a single subcutaneous dose (0.5 mg/kg)
of radiolabeled sumatriptan, the elimination half-life of radioactivity from
the eye was 15 days, suggesting that sumatriptan and its metabolites
bind to the melanin of the eye. The clinical significance of this binding
is unknown.
Pharmacokinetics
Pharmacokinetic parameters
following a 6-mg subcutaneous injection into the deltoid area of the arm in
9 males (mean age, 33 years; mean weight, 77 kg) were systemic
clearance: 1,194 ± 149 mL/min (mean ± S.D.),
distribution half-life: 15 ± 2 minutes, terminal half-life:
115 ± 19 minutes, and volume of distribution central compartment:
50 ± 8 liters. Of this dose, 22% ± 4% was
excreted in the urine as unchanged sumatriptan and 38% ± 7%
as the indole acetic acid metabolite.
After a single
6-mg subcutaneous manual injection into the deltoid area of the arm in 18
healthy males (age, 24 ± 6 years; weight, 70 kg), the
maximum serum concentration (Cmax) was (mean ± standard
deviation) 74 ± 15 ng/mL and the time to peak concentration
(Tmax) was 12 minutes after injection (range, 5 to 20 minutes). In this study, the same dose injected subcutaneously
in the thigh gave a Cmax of 61 ± 15 ng/mL by
manual injection versus 52 ± 15 ng/mL by autoinjector
techniques. The Tmaxoramount absorbed was not significantly altered
by either the site or technique of injection.
The bioavailability
of sumatriptan via subcutaneous site injection to 18 healthy male subjects
was 97% ± 16% of that obtained following intravenous injection.
Protein binding, determined by equilibrium dialysis over the concentration
range of 10 to 1,000 ng/mL, is low, approximately 14% to 21%. The effect
of sumatriptan on the protein binding of other drugs has not been evaluated.
Special Populations
Renal Impairment
The effect of renal impairment
on the pharmacokinetics of sumatriptan has not been examined, but little clinical
effect would be expected as sumatriptan is largely metabolized to an inactive
substance.
Hepatic Impairment
The effect of hepatic disease on the pharmacokinetics of
subcutaneously and orally administered sumatriptan has been evaluated. There
were no statistically significant differences in the pharmacokinetics of subcutaneously
administered sumatriptan in hepatically impaired patients compared to healthy
controls. However, the liver plays an important role in the presystemic clearance
of orally administered sumatriptan. Accordingly, the bioavailability of sumatriptan
following oral administration may be markedly increased in patients with liver
disease. In 1 small study of hepatically impaired patients (N = 8)
matched for sex, age, and weight with healthy subjects, the hepatically impaired
patients had an approximately 70% increase in AUC and Cmax and
a Tmax 40 minutes earlier compared to the healthy subjects.
Age
The pharmacokinetics of sumatriptan in the elderly (mean
age, 72 years, 2 males and 4 females) and in patients with
migraine (mean age, 38 years, 25 males and 155 females) were
similar to that in healthy male subjects (mean age, 30 years)(see PRECAUTIONS: Geriatric Use).
Race
The systemic clearance
and Cmax of sumatriptan were similar in black (n = 34)
and Caucasian (n = 38) healthy male subjects.
Drug Interactions
Monoamine Oxidase Inhibitors
In vitro studies with
human microsomes suggest that sumatriptan is metabolized by monoamine oxidase
(MAO), predominantly the A isoenzyme. In a study of 14 healthy females,
pretreatment with MAO-A inhibitor decreased the clearance of sumatriptan.
Under the conditions of this experiment, the result was a 2-fold increase
in the area under the sumatriptan plasma concentration x time curve (AUC),
corresponding to a 40% increase in elimination half-life. No significant effect
was seen with an MAO-B inhibitor.
Pharmacodynamics
Typical Physiologic Responses
Blood Pressure
(see WARNINGS: Increase in Blood Pressure)
Peripheral (small) Arteries
In healthy volunteers (N = 18), a study evaluating
the effects of sumatriptan on peripheral (small vessel) arterial reactivity
failed to detect a clinically significant increase in peripheral resistance.
Heart Rate
Transient increases in blood pressure observed in some patients
in clinical studies carried out during sumatriptan’s development as
a treatment for migraine were not accompanied by any clinically significant
changes in heart rate.
Respiratory Rate
Experience gained
during the clinical development of sumatriptan as a treatment for migraine
failed to detect an effect of the drug on respiratory rate.
CLINICAL TRIALS
Migraine
In US controlled clinical
trials enrolling more than 1,000 patients during migraine attacks who were
experiencing moderate or severe pain and 1 or more of the symptoms enumerated
in Table 2, onset of relief began as early as 10 minutes following a
6-mg IMITREX Injection. Smaller doses of sumatriptan may also prove effective,
although the proportion of patients obtaining adequate relief is decreased
and the latency to that relief is greater.
In 1 well-controlled
study where placebo (n = 62) was compared to 6 different doses of
IMITREX Injection (n = 30 each group) in a single-attack, parallel-group
design, the dose response relationship was found to be as shown in Table 1.
Table 1. Dose Response Relationship for Efficacy
|
IMITREX Dose (mg)
|
% Patients With Relief* at
10 Minutes
|
% Patients With Relief* at
30 Minutes
|
% Patients With Relief* at
1 Hour
|
% Patients With Relief* at
2 Hours
|
Adverse Events Incidence (%)
|
|
Placebo
|
5
|
15
|
24
|
21
|
55
|
|
1
|
10
|
40
|
43
|
40
|
63
|
|
2
|
7
|
23
|
57
|
43
|
63
|
|
3
|
17
|
47
|
57
|
60
|
77
|
|
4
|
13
|
37
|
50
|
57
|
80
|
|
6
|
10
|
63
|
73
|
70
|
83
|
|
8
|
23
|
57
|
80
|
83
|
93
|
In 2 US well-controlled clinical
trials in 1,104 migraine patients with moderate or severe migraine pain, the
onset of relief was rapid (less than 10 minutes) with IMITREX Injection
6 mg. Headache relief, as evidenced by a reduction in pain from severe
or moderately severe to mild or no headache, was achieved in 70% of the patients
within 1 hour of a single 6-mg subcutaneous dose of IMITREX Injection.
Headache relief was achieved in approximately 82% of patients within 2 hours,
and 65% of all patients were pain free within 2 hours.
Table
2 shows the 1- and 2-hour efficacy results for IMITREX Injection 6 mg.
Table 2. Efficacy Data From US Phase III Trials
|
1-Hour Data
|
Study 1
|
Study 2
|
|
Placebo (n = 190)
|
IMITREX 6 mg (n = 384)
|
Placebo (n = 180)
|
IMITREX 6 mg (n = 350)
|
|
Patients with pain relief (grade 0/1)
|
18%
|
70%*
|
26%
|
70%*
|
|
Patients with no pain
|
5%
|
48%*
|
13%
|
49%*
|
|
Patients without nausea
|
48%
|
73%*
|
50%
|
73%*
|
|
Patients without photophobia
|
23%
|
56%*
|
25%
|
58%*
|
|
Patients with little or no clinical disability†
|
34%
|
76%*
|
34%
|
76%*
|
|
2-Hour Data
|
Study 1
|
Study 2
|
|
Placebo‡
|
IMITREX 6 mg§
|
Placebo‡
|
IMITREX 6 mg§
|
|
Patients with pain relief (grade 0/1)
|
31%
|
81%*
|
39%
|
82%*
|
|
Patients with no pain
|
11%
|
63%*
|
19%
|
65%*
|
|
Patients without nausea
|
56%
|
82%*
|
63%
|
81%*
|
|
Patients without photophobia
|
31%
|
72%*
|
35%
|
71%*
|
|
Patients with little or no clinical disability†
|
42%
|
85%*
|
49%
|
84%*
|
IMITREX Injection
also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting
associated with migraine attacks. Similar efficacy was seen when patients
self-administered IMITREX Injection using an autoinjector.
The
efficacy of IMITREX Injection is unaffected by whether or not migraine is
associated with aura, duration of attack, gender or age of the patient, or
concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).
Cluster Headache
The efficacy of IMITREX Injection in the acute treatment
of cluster headache was demonstrated in 2 randomized, double-blind, placebo-controlled,
2-period crossover trials. Patients age 21 to 65 were enrolled and were instructed
to treat a moderate to very severe headache within 10 minutes of onset.
Headache relief was defined as a reduction in headache severity to mild or
no pain. In both trials, the proportion of individuals gaining relief at 10
or 15 minutes was significantly greater among patients receiving 6 mg
of IMITREX Injection compared to those who received placebo (see Table 3).
One study evaluated a 12-mg dose; there was no statistically significant difference
in outcome between patients randomized to the 6- and 12-mg doses.
Table 3. Efficacy Data From the Pivotal Cluster Headache
Studies
|
|
Study 1
|
Study 2
|
|
Placebo (n = 39)
|
IMITREX 6 mg (n = 39)
|
Placebo (n = 88)
|
IMITREX 6 mg (n = 92)
|
|
Patients with pain relief (no/mild)
|
|
|
|
|
|
5 minutes postinjection
|
8%
|
21%
|
7%
|
23%*
|
|
10 minutes postinjection
|
10%
|
49%*
|
25%
|
49%*
|
|
15 minutes postinjection
|
26%
|
74%*
|
35%
|
75%*
|
The
Kaplan-Meier (product limit) Survivorship Plot (Figure 1) provides an
estimate of the cumulative probability of a patient with a cluster headache
obtaining relief after being treated with either sumatriptan or placebo.
Figure 1. Time to Relief From Time of Injection*
The
plot was constructed with data from patients who either experienced relief
or did not require (request) rescue medication within a period of 2 hours
following treatment. As a consequence, the data in the plot are derived from
only a subset of the 258 headaches treated (rescue medication was required
in 52 of the 127 placebo-treated headaches and 18 of the 131 sumatriptan-treated
headaches).
Other data suggest that sumatriptan treatment
is not associated with an increase in early recurrence of headache, and that
treatment with sumatriptan has little effect on the incidence of latter-occurring
headaches (i.e., those occurring after 2, but before 18 or 24 hours).
INDICATIONS AND USAGE
IMITREX Injection is
indicated for 1) the acute treatment of migraine attacks with or without aura
and 2) the acute treatment of cluster headache episodes.
IMITREX
Injection is not for use in the management of hemiplegic or basilar migraine
(see CONTRAINDICATIONS).
CONTRAINDICATIONS
IMITREX Injection should not be
given intravenously because of its potential to cause coronary vasospasm.
IMITREX Injection
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
IMITREX Injection. 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: Other Vasospasm-Related Events and WARNINGS: Risk of
Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events).
Because IMITREX
Injection may increase blood pressure, it should not be given to patients
with uncontrolled hypertension.
IMITREX
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 IMITREX Injection and another 5-HT1 agonist.
IMITREX Injection should not be administered to patients
with hemiplegic or basilar migraine.
IMITREX Injection is contraindicated in patients with hypersensitivity
to sumatriptan or any of its components.
IMITREX Injection is contraindicated in patients with severe
hepatic impairment.
WARNINGS
IMITREX Injection should only
be used where a clear diagnosis of 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 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 aredetermined 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 IMITREX 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
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 IMITREX Injection
or IMITREX® (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 patientswith 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 CAD, the relationship is uncertain.
Premarketing Experience With Sumatriptan
Among the more than 1,900 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.
Of 6,348 patients with migraine
who participated in premarketing controlled and uncontrolled clinical trials
of oral sumatriptan, 2 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
approximately 4,000 patients with migraine who participated in premarketing
controlled and uncontrolled clinical trials of sumatriptan nasal spray, 1
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 IMITREX Injection or IMITREX
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 IMITREX 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 IMITREX.
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, the majority 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 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. Very rare reports of
transient and permanent blindness and significant partial vision loss have
been reported with the use of sumatriptan. Visual disorders may also be part
of a migraine attack.
Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake
Inhibitors and Serotonin Syndrome
Cases of life threatening serotonin syndrome have been reported
during combined use of selective serotonin reuptake inhibitors (SSRIs) or
serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans. If concomitant
treatment with IMITREX Injection is clinically warranted, careful observation
of the patient is advised, particularly during treatment initiation and dose
increases. 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).
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 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: Drug Interactions: Monoamine Oxidase Inhibitors).
Use in Women of Childbearing Potential
(see PRECAUTIONS: Pregnancy)
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, jaw, or neck tightness
is relatively common after administration of IMITREX Injection. Chest discomfort
and jaw or neck tightness have been reported following use of IMITREX Tablets
and have also been reported infrequently following the administration of IMITREX® (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: Risk of Myocardial Ischemia and/or Infarction
and Other Adverse Cardiac Events and WARNINGS: Other Vasospasm-Related Events).
IMITREX
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 conditions associated
with a lowered 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: Drug-Associated Cerebrovascular Events and Fatalities). 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 monitoring are offered, prescribers should
be aware of the possibility of long-term ophthalmologic effects (see CLINICAL
PHARMACOLOGY: Melanin Binding).
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: Corneal Opacities).
Patients who are advised to self-administer IMITREX 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 Patients
With the autoinjector, the needle penetrates approximately
1/4 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
INFORMATION at the end of this labeling for the text of the separate leaflet
provided for patients.
Laboratory Tests
No specific laboratory
tests are recommended for monitoring patients prior to and/or after treatment
with sumatriptan.
Drug Interactions
Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake
Inhibitors and Serotonin Syndrome
Cases of life-threatening serotonin syndrome have been reported
during combined use of SSRIs or SNRIs and triptans (see WARNINGS).
Migraine Prophylactic Medications
There is no evidence that concomitant use of migraine prophylactic
medications has any effect on the efficacy of sumatriptan. In 2 Phase III
trials in the US, a retrospective analysis of 282 patients who had been using
prophylactic drugs (verapamil n = 63, amitriptyline n = 57, propranolol n
= 94, for 45 other drugs n = 123) were compared to those who had not used
prophylaxis (N = 452). There were no differences in relief rates at 60 minutes
postdose for IMITREX Injection, whether or not prophylactic medications were
used.
Ergot-Containing Drugs
Ergot-containing drugs have been reported to cause prolonged
vasospastic reactions. Because there is a theoretical basis that these effects
may be additive, use of ergotamine-containing or ergot-type medications (like
dihydroergotamine or methysergide) and sumatriptan within 24 hours of
each other should be avoided (see CONTRAINDICATIONS).
Monoamine Oxidase-A Inhibitors
MAO-A inhibitors reduce sumatriptan clearance, significantly
increasing systemic exposure. Therefore, the use of sumatriptan in patients
receiving MAO-A inhibitors is not ordinarily recommended. If the clinical
situation warrants the combined use of sumatriptan and an MAOI, the dose of
sumatriptan employed should be reduced (see CLINICAL PHARMACOLOGY: Drug Interactions: Monoamine Oxidase Inhibitors and WARNINGS: Concomitant
Drug Use).
Drug/Laboratory Test Interactions
IMITREX is not known
to interfere with commonly employed clinical laboratory tests.
Carcinogenesis, Mutagenesis, 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 2 gene mutation assays (the Ames test and the in vitro mammalian
Chinese hamster V79/HGPRT assay). In 2 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/day.
The no-effect dose for this finding was approximately 8 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
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.
IMITREX 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 increased 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/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.
Pregnancy Registry
To monitor fetal outcomes of pregnant women exposed to IMITREX,
GlaxoSmithKline 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 following subcutaneous administration. Infant exposure
to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after
treatment with IMITREX Injection.
Pediatric Use
Safety and effectiveness
of IMITREX Injection in pediatric patients under 18 years of age have not
been established; therefore, IMITREX Injection is not recommended for use
in patients under 18 years of age.
Two controlled clinical
trials evaluating sumatriptan nasal spray (5 to 20 mg) in pediatric patients
aged 12 to 17 years enrolled a total of 1,248 adolescent migraineurs who treated
a single attack. The studies did not establish the efficacy of sumatriptan
nasal spray 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.
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.
Postmarketing
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 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: Risk of Myocardial Ischemia and/or
Infarction and Other Adverse Cardiac Events).
ADVERSE REACTIONS
Serious cardiac events, including
some that have been fatal, have occurred following the use of IMITREX Injection
or Tablets. These events are extremely rare and most have been reported in
patients with risk factors predictive of CAD. Events reported have included
coronary artery vasospasm, transient myocardial ischemia, myocardial infarction,
ventricular tachycardia, and ventricular fibrillation (see CONTRAINDICATIONS,
WARNINGS: Risk of Myocardial Ischemia and/or Infarction and Other Adverse
Cardiac Events, and PRECAUTIONS: General).
Significant
hypertensive episodes, including hypertensive crises, have been reported on
rare occasions in patients with or without a history of hypertension (see
WARNINGS: Increase in Blood Pressure).
Among patients
in clinical trials of subcutaneous IMITREX Injection (N = 6,218),
up to 3.5% of patients withdrew for reasons related to adverse events.
Incidence in Controlled Clinical Trials of Migraine Headache
Table 4 lists adverse events that occurred in 2 large US,
Phase III, placebo-controlled clinical trials in migraine patients following
either a single 6-mg dose of IMITREX Injection or placebo. Only events that
occurred at a frequency of 2% or more in groups treated with IMITREX Injection
6 mg and occurred at a frequency greater than the placebo group are included
in Table 4.
Table 4. Treatment Emergent
Adverse Experience Incidence in 2 Large Placebo-Controlled Migraine Clinical
Trials: Events Reported by at Least 2% of Patients Treated With IMITREX Injection
6 mg*
|
Adverse Event
|
Percent of Patients
Reporting
|
|
IMITREX Injection
6 mg
Subcutaneous
(n = 547)
|
Placebo
(n = 370)
|
|
Atypical sensations
|
42
|
9
|
|
Tingling
|
14
|
3
|
|
Warm/hot sensation
|
11
|
4
|
|
Burning sensation
|
7
|
<1
|
|
Feeling of heaviness
|
7
|
1
|
|
Pressure sensation
|
7
|
2
|
|
Feeling of tightness
|
5
|
<1
|
|
Numbness
|
5
|
2
|
|
Feeling strange
|
2
|
<1
|
|
Tight feeling in head
|
2
|
<1
|
|
Cardiovascular
|
|
|
|
Flushing
|
7
|
2
|
|
Chest discomfort
|
5
|
1
|
|
Tightness in chest
|
3
|
<1
|
|
Pressure in chest
|
2
|
<1
|
|
Ear, nose, and throat
|
|
|
|
Throat discomfort
|
3
|
<1
|
|
Discomfort: nasal cavity/sinuses
|
2
|
<1
|
|
Injection site reaction
|
59
|
24
|
|
Miscellaneous
|
|
|
|
Jaw discomfort
|
2
|
0
|
|
Musculoskeletal
|
|
|
|
Weakness
|
5
|
<1
|
|
Neck pain/stiffness
|
5
|
<1
|
|
Myalgia
|
2
|
<1
|
|
Neurological
|
|
|
|
Dizziness/vertigo
|
12
|
4
|
|
Drowsiness/sedation
|
3
|
2
|
|
Headache
|
2
|
<1
|
|
Skin
|
|
|
|
Sweating
|
2
|
1
|
The incidence
of adverse events in controlled clinical trials was not affected by gender
or age of the patients. There were insufficient data to assess the impact
of race on the incidence of adverse events.
Incidence in Controlled Trials of Cluster Headache
In the controlled clinical trials assessing sumatriptan’s
efficacy as a treatment for cluster headache, no new significant adverse events
associated with the use of sumatriptan were detected that had not already
been identified in association with the drug’s use in migraine.
Overall,
the frequency of adverse events reported in the studies of cluster headache
were generally lower. Exceptions include reports of paresthesia (5% IMITREX,
0% placebo), nausea and vomiting (4% IMITREX, 0% placebo), and bronchospasm
(1% IMITREX, 0% placebo).
Other Events Observed in Association With the Administration of IMITREX
Injection
In the paragraphs that
follow, the frequencies of less commonly reported adverse clinical events
are presented. Because the reports include events observed in open and uncontrolled
studies, the role of IMITREX Injection in their causation cannot be reliably
determined. Furthermore, variability associated with adverse event reporting,
the terminology used to describe adverse events, etc., limit the value of
the quantitative frequency estimates provided.
Event
frequencies are calculated as the number of patients reporting an event divided
by the total number of patients (N = 6,218) exposed to subcutaneous
IMITREX Injection. All reported events are included except those already listed
in the previous table, those too general to be informative, and those not
reasonably associated with the use of the drug. Events are further classified
within body system categories and enumerated in order of decreasing frequency
using the following definitions: frequent adverse events are defined as those
occurring in at least 1/100 patients, infrequent adverse events are those
occurring in 1/100 to 1/1,000 patients, and rare adverse events are those
occurring in fewer than 1/1,000 patients.
Cardiovascular
Infrequent were hypertension, hypotension, bradycardia,
tachycardia, palpitations, pulsating sensations, various transient ECG changes
(nonspecific ST or T wave changes, prolongation of PR or QTc intervals, sinus
arrhythmia, nonsustained ventricular premature beats, isolated junctional
ectopic beats, atrial ectopic beats, delayed activation of the right ventricle),
and syncope. Rare were pallor, arrhythmia, abnormal pulse, vasodilatation,
and Raynaud syndrome.
Endocrine and Metabolic
Infrequent was thirst. Rare were polydipsia and dehydration.
Eye
Frequent was vision alterations. Infrequent was irritation
of the eye.
Gastrointestinal
Frequent were abdominal discomfort and dysphagia. Infrequent
were gastroesophageal reflux and diarrhea. Rare were peptic ulcer, retching,
flatulence/eructation, and gallstones.
Musculoskeletal
Frequent were muscle cramps. Infrequent were various joint
disturbances (pain, stiffness, swelling, ache). Rare were muscle stiffness,
need to flex calf muscles, backache, muscle tiredness, and swelling of the
extremities.
Neurological
Frequent was anxiety. Infrequent were mental confusion,
euphoria, agitation, relaxation, chills, sensation of lightness, tremor, shivering,
disturbances of taste, prickling sensations, paresthesia, stinging sensations,
facial pain, photophobia, and lacrimation. Rare were transient hemiplegia,
hysteria, globus hystericus, intoxication, depression, myoclonia, monoplegia/diplegia,
sleep disturbance, difficulties in concentration, disturbances of smell, hyperesthesia,
dysesthesia, simultaneous hot and cold sensations, tickling sensations, dysarthria,
yawning, reduced appetite, hunger, and dystonia.
Respiratory
Infrequent was dyspnea. Rare were influenza, diseases of
the lower respiratory tract, and hiccoughs.
Skin
Infrequent were erythema, pruritus, and skin rashes and
eruptions. Rare was skin tenderness.
Urogenital
Rare were dysuria, frequency, dysmenorrhea, and renal calculus.
Miscellaneous
Infrequent were
miscellaneous laboratory abnormalities, including minor disturbances in liver
function tests, “serotonin agonist effect,” and hypersensitivity
to various agents. Rare was fever.
Other Events Observed in the Clinical Development of IMITREX
The following adverse events occurred in clinical trials
with IMITREX Tablets and IMITREX Nasal Spray. Because the reports include
events observed in open and uncontrolled studies, the role of IMITREX in their
causation cannot be reliably determined. All reported events are included
except those already listed, those too general to be informative, and those
not reasonably associated with the use of the drug.
Breasts
Breast swelling, cysts, disorder of breasts, lumps, masses
of breasts, nipple discharge, primary malignant breast neoplasm, and tenderness.
Cardiovascular
Abdominal aortic
aneurysm, angina, atherosclerosis, cerebral ischemia, cerebrovascular lesion,
heart block, peripheral cyanosis, phlebitis, thrombosis, and transient myocardial
ischemia.
Ear, Nose, and Throat
Allergic rhinitis; disorder of nasal cavity/sinuses; ear,
nose, and throat hemorrhage; ear infection; external otitis; feeling of fullness
in the ear(s); hearing disturbances; hearing loss; Meniere disease; nasal
inflammation; otalgia; sensitivity to noise; sinusitis; tinnitus; and upper
respiratory inflammation.
Endocrine and Metabolic
Elevated thyrotropin stimulating hormone (TSH) levels; endocrine
cysts, lumps, and masses; fluid disturbances; galactorrhea; hyperglycemia;
hypoglycemia; hypothyroidism; weight gain; and weight loss.
Eye
Accommodation disorders, blindness and low vision, conjunctivitis,
disorders of sclera, external ocular muscle disorders, eye edema and swelling,
eye hemorrhage, eye itching, eye pain, keratitis, mydriasis, and visual disturbances.
Gastrointestinal
Abdominal distention, colitis, constipation, dental pain,
dyspeptic symptoms, feelings of gastrointestinal pressure, gastric symptoms,
gastritis, gastroenteritis, gastrointestinal bleeding, gastrointestinal pain,
hematemesis, hypersalivation, hyposalivation, intestinal obstruction, melena,
nausea and/or vomiting, oral itching and irritation, pancreatitis, salivary
gland swelling, and swallowing disorders.
Hematological Disorders
Anemia.
Mouth and Teeth
Disorder of mouth and tongue (e.g., burning of tongue, numbness
of tongue, dry mouth).
Musculoskeletal
Acquired musculoskeletal deformity, arthralgia and articular
rheumatitis, arthritis, intervertebral disc disorder, muscle atrophy, muscle
tightness and rigidity, musculoskeletal inflammation, and tetany.
Neurological
Apathy, aggressiveness, bad/unusual taste, bradylogia, cluster
headache, convulsions, depressive disorders, detachment, disturbance of emotions,
drug abuse, facial paralysis, hallucinations, heat sensitivity, incoordination,
increased alertness, memory disturbance, migraine, motor dysfunction, neoplasm
of pituitary, neuralgia, neurotic disorders, paralysis, personality change,
phobia, phonophobia, psychomotor disorders, radiculopathy, raised intracranial
pressure, rigidity, stress, syncope, suicide, and twitching.
Respiratory
Asthma, breathing disorders, bronchitis, cough, and lower
respiratory tract infection.
Skin
Dry/scaly skin, eczema, herpes, seborrheic dermatitis, skin
nodules, tightness of skin, and wrinkling of skin.
Urogenital
Abnormal menstrual cycle, abortion, bladder inflammation,
endometriosis, hematuria, increased urination, inflammation of fallopian tubes,
intermenstrual bleeding, menstruation symptoms, micturition disorders, urethritis,
and urinary infections.
Miscellaneous
Contusions, difficulty in walking, edema, hematoma, hypersensitivity,
fever, fluid retention, lymphadenopathy, overdose, speech disturbance, swelling
of extremities, swelling of face, and voice disturbances.
Pain and Other Pressure Sensations
Chest pain and/or heaviness, neck/throat/jaw pain/tightness/pressure,
and pain (location specified).
Postmarketing Experience (Reports for Subcutaneous or Oral Sumatriptan)
The following section enumerates potentially important adverse
events that have occurred in clinical practice and that have been reported
spontaneously to various surveillance systems. The events enumerated represent
reports arising from both domestic and nondomestic use of oral or subcutaneous
dosage forms of sumatriptan. The events enumerated include all except those
already listed in the ADVERSE REACTIONS section above or those too general
to be informative. Because the reports cite events reported spontaneously
from worldwide postmarketing experience, frequency of events and the role
of IMITREX Injection in their causation cannot be reliably determined. It
is assumed, however, that systemic reactions following sumatriptan use are
likely to be similar regardless of route of administration.
Blood
Hemolytic anemia, pancytopenia, thrombocytopenia.
Cardiovascular
Atrial fibrillation, cardiomyopathy, colonic ischemia (see
WARNINGS), Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis.
Ear, Nose, and Throat
Deafness.
Eye
Ischemic optic neuropathy, retinal artery occlusion, retinal
vein thrombosis, loss of vision.
Gastrointestinal
Ischemic colitis with rectal bleeding (see WARNINGS), xerostomia.
Hepatic
Elevated liver function tests.
Neurological
Central nervous system vasculitis, cerebrovascular accident,
dysphasia, serotonin syndrome, subarachnoid hemorrhage.
Non-Site Specific
Angioneurotic edema, cyanosis, death (see WARNINGS), temporal
arteritis.
Psychiatry
Panic disorder.
Respiratory
Bronchospasm in patients with and without a history of asthma.
Skin
Exacerbation of sunburn, hypersensitivity reactions (allergic
vasculitis, erythema, pruritus, rash, shortness of breath, urticaria; in addition,
severe anaphylaxis/anaphylactoid reactions have been reported [see WARNINGS:
Hypersensitivity]), photosensitivity. Following subcutaneous administration
of sumatriptan, pain, redness, stinging, induration, swelling, contusion,
subcutaneous bleeding, and, on rare occasions, lipoatrophy (depression in
the skin) or lipohypertrophy (enlargement or thickening of tissue) have been
reported.
Urogenital
Acute renal failure.
DRUG ABUSE AND DEPENDENCE
The abuse potential of
IMITREX Injection cannot be fully delineated in advance of extensive marketing
experience. One clinical study enrolling 12 patients with a history of substance
abuse failed to induce subjective behavior and/or physiologic response ordinarily
associated with drugs that have an established potential for abuse.
OVERDOSAGE
Patients (N = 269) have received single injections
of 8 to 12 mg without significant adverse effects. Volunteers (N = 47)
have received single subcutaneous doses of up to 16 mg without serious
adverse events.
No gross overdoses in clinical practice
have been reported. Coronary vasospasm was observed after intravenous administration
of IMITREX Injection (see CONTRAINDICATIONS). Overdoses would be expected
from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly
cause convulsions, tremor, inactivity, erythema of the extremities, reduced
respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation,
hair loss, and scab formation), and paralysis. The half-life of elimination
of sumatriptan is about 2 hours (see CLINICAL PHARMACOLOGY: Pharmacokinetics),
and therefore monitoring of patients after overdose with IMITREX Injection
should continue while symptoms or signs persist, and for at least 10 hours.
It
is unknown what effect hemodialysis or peritoneal dialysis has on the serum
concentrations of sumatriptan.
DOSAGE AND ADMINISTRATION
The maximum single recommended
adult dose of IMITREX Injection is 6 mg injected subcutaneously. If side
effects are dose limiting, then lower doses may be used (see Table 1).
The
maximum recommended dose that may be given in 24 hours is two 6-mg injections
separated by at least 1 hour. Controlled clinical trials have failed
to show that clear benefit is associated with the administration of a second
6-mg dose in patients who have failed to respond to a first injection.
In
patients receiving MAO inhibitors, decreased doses of sumatriptan should be
considered (see WARNINGS: Concomitant Drug Use and CLINICAL PHARMACOLOGY:
Drug Interactions: Monoamine Oxidase Inhibitors).
An autoinjection device is available
for use with the 4- and 6-mg prefilled syringe cartridges to facilitate self-administration
in patients using the 4- or 6-mg dose. With this device, the needle penetrates
approximately 1/4 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.
In
patients receiving doses other than 4 or 6 mg, only the 6-mg single-dose
vial dosage form should be used. Parenteral drug products should be inspected
visually for particulate matter and discoloration before administration whenever
solution and container permit.
HOW SUPPLIED
IMITREX Injection contains sumatriptan (base) as the succinate
salt and is supplied as a clear, colorless to pale yellow, sterile, nonpyrogenic
solution as follows:
(NDC 0173-0739-00) IMITREX STATdose
System®, 4 mg, containing 2 prefilled single-dose syringe
cartridges, 1 IMITREX STATdose Pen®, and instructions for
use.
(NDC 0173-0739-02) Two 4-mg single-dose prefilled
syringe cartridges for use with IMITREX STATdose System.
(NDC
0173-0479-00) IMITREX STATdose System, 6 mg, containing 2 prefilled single-dose
syringe cartridges, 1 IMITREX STATdose Pen, and instructions for use.
(NDC
0173-0478-00) Two 6-mg single-dose prefilled syringe cartridges for use with
IMITREX STATdose System.
(NDC 0173-0449-02) IMITREX
Injection single-dose vial (6 mg/0.5 mL) in cartons containing 5
vials.
Store between 2°
and 30°C (36° and 86°F). Protect from light.
PATIENT INFORMATION
The following wording is contained in a separate leaflet
provided for patients.
Information
for the Patient
IMITREX® (sumatriptan
succinate) Injection
Read this leaflet carefully
before you start to take IMITREX Injection. Keep the leaflet for reference
because it gives you a summary of important information about IMITREX Injection.
Read
the leaflet that comes with each refill of your prescription because there
may be new information.
This leaflet does not have all
the information about IMITREX Injection. Ask your healthcare provider for
more information or advice.
What
is IMITREX Injection?
IMITREX Injection is
a 5-HT1 agonist. It is also called a “triptan.” You
should use it only if you have a prescription.
IMITREX
Injection is used to relieve your migraine or cluster headache. IMITREX Injection
is not used to prevent attacks or reduce the number of attacks you have. Use
IMITREX Injection only to treat an actual migraine or cluster headache attack.
The
decision to use IMITREX Injection is one that you and your healthcare provider
should make together, taking into account your personal needs and health.
Talk to your healthcare provider before taking IMITREX Injection
- Risk factors for heart disease:
Tell
your healthcare provider if you have risk factors for heart disease such as:
- high blood pressure,
- high cholesterol,
- obesity,
- diabetes,
- smoking,
- strong family history of heart disease,
- you are postmenopausal, or
- you are a male over 40 years of age.
If you do have risk factors for heart disease, your healthcare
provider should check you for heart disease to see if IMITREX is right for
you.
Although most of the people who have taken IMITREX
have not had any serious side effects, some have had serious heart problems.
Deaths have been reported, but these were rare considering the extensive worldwide
use of IMITREX. Usually, serious problems happened in people with known heart
diseases. It was not clear whether IMITREX had anything to do with these deaths.
- Important questions to consider before taking
IMITREX Injection:
If the answer
to any of the following questions is YES or
if you do not know the answer, then please talk with your healthcare provider
before you use IMITREX Injection.
- Are you pregnant? Do you think you might be pregnant? Are you trying
to become pregnant? Are you using inadequate contraception? Are you breastfeeding?
- Do you have any chest pain, heart disease, shortness of breath, or irregular
heartbeats? Have you had a heart attack?
- Do you have risk factors for heart disease (such as high blood pressure,
high cholesterol, obesity, diabetes, smoking, strong family history of heart
disease, or you are postmenopausal or a male over 40)?
- Have you had a stroke, transient ischemic attacks (TIAs), or Raynaud
syndrome?
- Do you have high blood pressure?
- Have you ever had to stop taking this or any other medicine because
of an allergy or other problems?
- Are you taking any other migraine medicines, including other 5 HT1 agonists
(triptans) or any other medicines containing ergotamine, dihydroergotamine,
or methysergide?
- Are you taking any medicine for depression such as monoamine oxidase
inhibitors, selective serotonin reuptake inhibitors (SSRIs), or serotonin
norepinephrine reuptake inhibitors (SNRIs)?
- Have you had, or do you have, any disease of the liver or kidney?
- Have you had, or do you have, epilepsy or seizures?
- Is this headache different from your usual migraine attacks?
Remember, if you answered YES to any of the above questions, then talk with your healthcare
provider about it.
Important points about IMITREX
Injection
- The use of IMITREX Injection during pregnancy:
Do not use IMITREX Injection
if you are pregnant, think you might be pregnant, are trying to become pregnant,
or are not using adequate contraception unless you have talked with your healthcare
provider about this.
- How to use IMITREX Injection:
For
adults, the usual dose is a single injection given just below the skin. You
should give an injection as soon as the symptoms of your migraine start, but
it may be given at any time during an attack.
You may
give a second injection if your migraine symptoms come back. If your symptoms
do not get better after the first injection, do not give a second injection
for the same attack without first talking with your healthcare provider. Do
not give more than two 6-mg doses in any 24-hour period. Allow at least 1
hour between each dose.
- What to do if you take an overdose:
If
you have taken more medicine than has been prescribed for you, contact either
your healthcare provider, hospital emergency department, or nearest poison
control center immediately.
- How to store your medicine:
Keep
your medicine in a safe place where children cannot reach it. It may be harmful
to children.
Store your medicine away from heat and
light. Keep your medicine in the packaging provided. Do not store at temperatures
above 86°F (30°C).
The expiration date of
your medicine is printed on the back of the Cartridge Pack. If your medicine
has expired, throw it away as instructed. Do not throw away your IMITREX STATdose
Pen®.
If your healthcare provider decides to stop
your treatment, do not keep any leftover medicine unless your healthcare provider
tells you to. Throw away your medicine as instructed.
Some possible side effects of
MITREX Injection
-
Some patients feel pain or tightness in the chest or throat
when using IMITREX Injection. If this happens to you, then discuss it with
your healthcare provider before using any more IMITREX Injection. If the chest
pain is severe or does not go away, call your healthcare provider right away.
-
Call your healthcare provider right away if you have sudden
and/or severe abdominal pain following IMITREX Injection.
-
Some people may have a reaction called serotonin syndrome
when they use certain types of antidepressants, SSRIs or SNRIs, while taking
IMITREX Injection. Symptoms may include confusion, hallucinations, fast heartbeat,
feeling faint, fever, sweating, muscle spasm, difficulty walking, and/or diarrhea.
Call your doctor immediately if you have any of these symptoms after taking
IMITREX Injection.
-
Shortness of breath; wheeziness; heart throbbing; swelling
of eyelids, face, or lips; or a skin rash, skin lumps, or hives happens rarely.
If it happens to you, then tell your healthcare provider right away. Do not
take any more IMITREX Injection unless your healthcare provider tells you
to.
-
Some people may feel tingling, heat, flushing (redness of
face lasting a short time), heaviness, or pressure after using IMITREX Injection.
A few people may feel drowsy, dizzy, tired, or sick. If you have any of these
symptoms, tell your healthcare provider at your next visit.
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You may have pain or redness at the site of injection, but
this usually lasts less than an hour.
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If you feel unwell in any other way or have any symptoms
that you do not understand, you should contact your healthcare provider right
away.
GlaxoSmithKline
Research
Triangle Park, NC 27709
©2006, GlaxoSmithKline.
All rights reserved.
November 2006 RL-2316
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| IMITREX (sumatriptan succinate) |
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Revised: 12/2006GlaxoSmithKline