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Name:Sumatriptan Succinate
Manufacturer:Mylan Pharmaceuticals Inc.
Category:Prescription Marketed Drugs


SUMATRIPTAN SUCCINATE - sumatriptan succinate tablet, film coated 
Mylan Pharmaceuticals Inc.

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DESCRIPTION

Sumatriptan succinate tablets contain sumatriptan (as the succinate), a selective 5-hydroxytryptamine1 receptor subtype agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methylindole-5-methanesulfonamide succinate (1:1), and it has the following structure:

Structural Formula

The molecular 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. Each sumatriptan succinate tablet for oral administration contains 35 mg, 70 mg or 140 mg of sumatriptan succinate, USP equivalent to 25 mg, 50 mg or 100 mg of sumatriptan, respectively. Each tablet also contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, povidone, sodium lauryl sulfate, titanium dioxide and triacetin.

CLINICAL PHARMACOLOGY

Mechanism of Action

Sumatriptan is an agonist for a vascular 5-hydroxytryptamine1 receptor subtype (probably a member of the 5-HT1D family) having only a weak affinity for 5-HT1A, 5-HT5A and 5-HT7 receptors and no significant affinity (as measured using standard radioligand binding assays) or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2- or beta-adrenergic; dopamine1; dopamine2; muscarinic; or benzodiazepine receptors.

The vascular 5-HT1 receptor subtype that sumatriptan activates is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of human dura mater and mediates vasoconstriction. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that sumatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels. Such an action may also contribute to the antimigrainous effect of sumatriptan in humans.

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.

Pharmacokinetics

The mean maximum concentration following oral dosing with 25 mg is 18 ng/mL (range, 7 to 47 ng/mL) and 51 ng/mL (range, 28 to 100 ng/mL) following oral dosing with 100 mg of sumatriptan. This compares with a Cmax of 5 and 16 ng/mL following dosing with a 5 mg and 20 mg intranasal dose, respectively. The mean Cmax following a 6 mg subcutaneous injection is 71 ng/mL (range, 49 to 110 ng/mL). The bioavailability is approximately 15%, primarily due to presystemic metabolism and partly due to incomplete absorption. The Cmax is similar during a migraine attack and during a migraine-free period, but the Tmax is slightly later during the attack, approximately 2.5 hours compared to 2 hours. When given as a single dose, sumatriptan displays dose proportionality in its extent of absorption (area under the curve [AUC]) over the dose range of 25 mg to 200 mg, but the Cmax after 100 mg is approximately 25% less than expected (based on the 25 mg dose).

A food effect study involving administration of sumatriptan succinate tablets 100 mg to healthy volunteers under fasting conditions and with a high-fat meal indicated that the Cmax and AUC were increased by 15% and 12%, respectively, when administered in the fed state.

Plasma protein binding is low (14% to 21%). The effect of sumatriptan on the protein binding of other drugs has not been evaluated, but would be expected to be minor, given the low rate of protein binding. The apparent volume of distribution is 2.4 L/kg.

The elimination half-life of sumatriptan is approximately 2.5 hours. Radiolabeled 14C-sumatriptan administered orally is largely renally excreted (about 60%) with about 40% found in the feces. Most of the radiolabeled compound excreted in the urine is the major metabolite, indole acetic acid (IAA), which is inactive, or the IAA glucuronide. Only 3% of the dose can be recovered as unchanged sumatriptan.

In vitro studies with human microsomes suggest that sumatriptan is metabolized by monoamine oxidase (MAO), predominantly the A isoenzyme, and inhibitors of that enzyme may alter sumatriptan pharmacokinetics to increase systemic exposure. No significant effect was seen with an MAO-B inhibitor (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS: Drug Interactions).

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 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 one 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 (see DOSAGE AND ADMINISTRATION).

Age

The pharmacokinetics of oral 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).

Gender

In a study comparing females to males, no pharmacokinetic differences were observed between genders for AUC, Cmax, Tmax and half-life.

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

Treatment with MAO-A inhibitors generally leads to an increase of sumatriptan plasma levels (see CONTRAINDICATIONS and PRECAUTIONS).

Due to gut and hepatic metabolic first-pass effects, the increase of systemic exposure after coadministration of an MAO-A inhibitor with oral sumatriptan is greater than after coadministration of the monoamine oxidase inhibitors (MAOI) with subcutaneous sumatriptan. In a study of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous 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. This interaction was not evident with an MAO-B inhibitor.

A small study evaluating the effect of pretreatment with an MAO-A inhibitor on the bioavailability from a 25 mg oral sumatriptan tablet resulted in an approximately 7-fold increase in systemic exposure.

Alcohol

Alcohol consumed 30 minutes prior to sumatriptan ingestion had no effect on the pharmacokinetics of sumatriptan.

CLINICAL STUDIES

The efficacy of sumatriptan succinate tablets in the acute treatment of migraine headaches was demonstrated in three randomized, double-blind, placebo-controlled studies. Patients enrolled in these three studies were predominately female (87%) and Caucasian (97%), with a mean age of 40 years (range, 18 to 65 years). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 4 hours after dosing. Associated symptoms such as nausea, photophobia and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours post-dose. A second dose of sumatriptan succinate tablets or other medication was allowed 4 to 24 hours after the initial treatment for recurrent headache. Acetaminophen was offered to patients in Studies 2 and 3 beginning at 2 hours after initial treatment if the migraine pain had not improved or worsened. Additional medications were allowed 4 to 24 hours after the initial treatment for recurrent headache or as rescue in all three studies. The frequency and time to use of these additional treatments were also determined. In all studies, doses of 25 mg, 50 mg and 100 mg were compared to placebo in the treatment of migraine attacks. In one study, doses of 25 mg, 50 mg and 100 mg were also compared to each other.

In all three trials, the percentage of patients achieving headache response 2 and 4 hours after treatment was significantly greater among patients receiving sumatriptan succinate tablets at all doses compared to those who received placebo. In one of the three studies, there was a statistically significant greater percentage of patients with headache response at 2 and 4 hours in the 50 mg or 100 mg group when compared to the 25 mg dose groups. There were no statistically significant differences between the 50 mg and 100 mg dose groups in any study. The results from the three controlled clinical trials are summarized in Table 1.

Comparisons of drug performance based upon results obtained in different clinical trials are never reliable. Because studies are conducted at different times, with different samples of patients, by different investigators, employing different criteria and/or different interpretations of the same criteria, under different conditions (dose, dosing regimen, etc.), quantitative estimates of treatment response and the timing of response may be expected to vary considerably from study to study.

Table 1: Percentage of Patients with Headache Response (No or Mild Pain) 2 and 4 Hours Following Treatment
*
p < 0.05 in comparison with placebo
p < 0.05 in comparison with 25 mg
      Placebo     Sumatriptan
Succinate Tablets
25 mg
Sumatriptan
Succinate Tablets
50 mg
Sumatriptan
Succinate Tablets
100 mg
  2 hr 4 hr 2 hr 4 hr 2 hr 4 hr 2 hr 4 hr
   Study 1    27% 38% 52%* 67%* 61%* 78%*† 62%*† 79%*†
  (N = 94) (N = 298) (N = 296) (N = 296)
   Study 2    26% 38% 52%* 70%* 50%* 68%* 56%* 71%*
  (N = 65) (N = 66) (N = 62) (N = 66)
   Study 3    17% 19% 52%* 65%* 54%* 72%* 57%* 78%*
  (N = 47) (N = 48) (N = 46) (N = 46)

The estimated probability of achieving an initial headache response over the 4 hours following treatment is depicted in Figure 1.

Sumatriptan Figure 1

Figure 1: Estimated Probability of Achieving Initial Headache Response within 240 Minutes*

* The figure shows the probability over time of obtaining headache response (no or mild pain) following treatment with sumatriptan. The averages displayed are based on pooled data from the three clinical controlled trials providing evidence of efficacy. Kaplan-Meier plot with patients not achieving response and/or taking rescue within 240 minutes censored to 240 minutes.

For patients with migraine-associated nausea, photophobia and/or phonophobia at baseline, there was a lower incidence of these symptoms at 2 hours (Study 1) and at 4 hours (Studies 1, 2 and 3) following administration of sumatriptan succinate tablets compared to placebo.

As early as 2 hours in Studies 2 and 3 or 4 hours in Study 1, through 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2.

Sumatriptan Figure 2

Figure 2: The Estimated Probability of Patients Taking a Second Dose or Other Medication for Migraine Over the 24 Hours Following the Initial Dose of Study Treatment*

*Kaplan-Meier plot based on data obtained in the three clinical controlled trials providing evidence of efficacy with patients not using additional treatments censored to 24 hours. Plot also includes patients who had no response to the initial dose. No remedication was allowed within 2 hours post-dose.

There is evidence that doses above 50 mg do not provide a greater effect than 50 mg. There was no evidence to suggest that treatment with sumatriptan was associated with an increase in the severity of recurrent headaches. The efficacy of sumatriptan succinate tablets was unaffected by presence of aura; duration of headache prior to treatment; gender, age or weight of the patient; relationship to menses; or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants). There were insufficient data to assess the impact of race on efficacy.

INDICATIONS AND USAGE

Sumatriptan succinate tablets are indicated for the acute treatment of migraine attacks with or without aura in adults.

Sumatriptan succinate tablets are not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see CONTRAINDICATIONS). Safety and effectiveness of sumatriptan succinate tablets have not been established for cluster headache, which is present in an older, predominantly male population.

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 PRECAUTIONS: 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 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 tablets 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 6,348 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 1,900 patients with migraine who participated in premarketing controlled clinical trials of subcutaneous sumatriptan, there were eight patients who sustained clinical events during or shortly after receiving sumatriptan that may have reflected coronary artery vasospasm. Six of these eight patients had ECG changes consistent with transient ischemia, but without accompanying clinical symptoms or signs. Of these eight patients, four had either findings suggestive of CAD or risk factors predictive of CAD prior to study enrollment.

Among approximately 4,000 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.

Post-Marketing Experience with Sumatriptan

Serious cardiovascular events, some resulting in death, have been reported in association with the use of sumatriptan succinate injection or sumatriptan succinate tablets. The uncontrolled nature of post-marketing 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 and the onset of the clinical event, the less likely the association is to be causative. Accordingly, interest has focused on events beginning within one hour of the administration of sumatriptan.

Cardiac events that have been observed to have onset within one 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 one 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 sumatriptan 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. 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.

Serotonin Syndrome

The development of a potentially life threatening serotonin syndrome may occur with triptans, including treatment with sumatriptan, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (e.g., venlafaxine, duloxetine) 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 7-fold 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 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 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 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.

Overuse of acute migraine treatments has been associated with the exacerbation of headache (medication overuse headache) in susceptible patients. Withdrawal of the treatment may be necessary.

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 an 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 TOXICOLOGY).

Information for Patients

See PATIENT INFORMATION at the end of this labeling for the text of the separate leaflet provided for patients.

Patients should be cautioned about the risk of serotonin syndrome with the use of sumatriptan or other triptans, especially during combined use with SSRIs or SNRIs.

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).

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 succinate tablets in patients receiving MAO-A inhibitors is contraindicated (see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS).

Drug/Laboratory Test Interactions

Sumatriptan succinate tablets are not known to interfere with commonly employed clinical laboratory tests.

Carcinogenesis, Mutagenesis, 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/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/day, reduced from 360 mg/kg/day during week 21) was approximately 15 times the maximum recommended single human oral 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/day. The highest no-effect dose for this finding was 5 mg/kg/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/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

Teratogenic Effects: Pregnancy Category C

In reproductive toxicity studies in rats and rabbits, oral treatment with sumatriptan was associated with embryolethality, 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 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/day, and in the intravenous studies this dose was 2 mg/kg/day. The mechanism of the embryolethality is not known. The highest no-effect dose for embryolethality by the oral route was 50 mg/kg/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/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 12.5mg/kg/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/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/day or higher. The highest no-effect dose was approximately 60 mg/kg/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/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/day. The highest no-effect dose was 50 mg/kg/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/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/day or higher. The highest no-effect dose for this effect was approximately 60 mg/kg/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/day. The highest no-effect dose for this finding was 100 mg/kg/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/day, the highest dose tested, which is equivalent to 8 times the maximum single recommended human oral dose of 100 mg on a mg/m2 basis.

Nursing Mothers

Sumatriptan is excreted in human breast milk following subcutaneous administration. Infant exposure to sumatriptan can be minimized by avoiding breast-feeding for 12 hours after treatment with sumatriptan succinate tablets.

Pediatric Use

Safety and effectiveness of sumatriptan succinate tablets in pediatric patients under 18 years of age have not been established; therefore, sumatriptan succinate tablets are not recommended for use in patients under 18 years of age.

Two controlled clinical trials evaluating sumatriptan nasal spray (5 mg 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 (two single attack studies, three multiple attack studies) evaluating oral sumatriptan (25 mg to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 adolescent migraineurs. These studies did not establish the efficacy of oral sumatriptan compared to placebo in the treatment of migraine in adolescents. Adverse events observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse events in these patients appeared to be both dose and age dependent, with younger patients reporting events more commonly than older adolescents.

Post-marketing experience documents that serious adverse events have occurred in the pediatric population after use of subcutaneous, oral and/or intranasal sumatriptan. These reports include events similar in nature to those reported rarely in adults, including stroke, visual loss and death. A myocardial infarction has been reported in a 14 year old male following the use of oral sumatriptan; clinical signs occurred within one 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).

ADVERSE REACTIONS

Serious cardiac events, including some that have been fatal, have occurred following the use sumatriptan succinate injection or sumatriptan succinate 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 and PRECAUTIONS).

Significant hypertensive episodes, including hypertensive crises, have been reported on rare occasions in patients with or without a history of hypertension (see WARNINGS).

Incidence in Controlled Clinical Trials

Table 2 lists adverse events that occurred in placebo-controlled clinical trials in patients who took at least one dose of study drug. Only events that occurred at a frequency of 2% or more in any group treated with sumatriptan succinate tablets and were more frequent in that group than in the placebo group are included in Table 2. The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.

Table 2. Treatment-Emergent Adverse Events Reported by at Least 2% of Patients in Controlled Migraine Trials*
*
Events that occurred at a frequency of 2% or more in the group treated with sumatriptan succinate tablets and that occurred more frequently in that group than the placebo group.
Adverse Event Type Percent of Patients Reporting
Placebo
(N = 309)
Sumatriptan
Succinate Tablets
25 mg
(N = 417)
Sumatriptan
Succinate Tablets
50 mg
(N = 771)
Sumatriptan
Succinate Tablets
100 mg
(N = 437)
Atypical sensations 4% 5% 6% 6%
   Paresthesia (all types) 2% 3% 5% 3%
   Sensation warm/cold 2% 3% 2% 3%
Pain and other pressure sensations 4% 6% 6% 8%
   Chest-pain/tightness/pressure and/or heaviness 1% 1% 2% 2%
   Neck/throat/jaw-pain/tightness/pressure < 1% < 1% 2% 3%
   Pain - location specified 1% 2% 1% 1%
   Other - pressure/tightness/heaviness 2% 1% 1% 3%
Neurological        
   Vertigo < 1% < 1% < 1% 2%
Other         
   Malaise/fatigue < 1% 2% 2% 3%

Other events that occurred in more than 1% of patients receiving sumatriptan succinate tablets and at least as often on placebo included nausea and/or vomiting, migraine, headache, hyposalivation, dizziness and drowsiness/sleepiness.

Sumatriptan succinate tablets are generally well tolerated. Across all doses, most adverse reactions were mild and transient and did not lead to long-lasting effects. 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.

Other Events Observed in Association with the Administration of Sumatriptan Succinate Tablets

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 sumatriptan succinate tablets 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 quantitative frequency estimates provided. Event frequencies are calculated as the number of patients who used sumatriptan succinate tablets (25 mg, 50 mg or 100 mg) and reported an event divided by the total number of patients (N = 6,348) exposed to sumatriptan succinate tablets. 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.

Atypical Sensations: Frequent were burning sensation and numbness. Infrequent was tight feeling in head. Rare were dysesthesia.

Cardiovascular: Frequent were palpitations, syncope, decreased blood pressure and increased blood pressure. Infrequent were arrhythmia, changes in ECG, hypertension, hypotension, pallor, pulsating sensations and tachycardia. Rare were angina, atherosclerosis, bradycardia, cerebral ischemia, cerebrovascular lesion, heart block, peripheral cyanosis, thrombosis, transient myocardial ischemia and vasodilation.

Ear, Nose and Throat: Frequent were sinusitis, tinnitus; allergic rhinitis; upper respiratory inflammation; ear, nose and throat hemorrhage; external otitis; hearing loss; nasal inflammation; and sensitivity to noise. Infrequent were hearing disturbances and otalgia. Rare was feeling of fullness in the ear(s).

Endocrine and Metabolic: Infrequent was thirst. Rare were elevated thyrotropin stimulating hormone (TSH) levels; galactorrhea; hyperglycemia; hypoglycemia; hypothyroidism; polydipsia; weight gain; weight loss; endocrine cysts, lumps and masses; and fluid disturbances.

Eye: Rare were disorders of sclera, mydriasis, blindness and low vision, visual disturbances, eye edema and swelling, eye irritation and itching, accommodation disorders, external ocular muscle disorders, eye hemorrhage, eye pain and keratitis and conjunctivitis.

Gastrointestinal: Frequent were diarrhea and gastric symptoms. Infrequent were constipation, dysphagia and gastroesophageal reflux. Rare were gastrointestinal bleeding, hematemesis, melena, peptic ulcer, gastrointestinal pain, dyspeptic symptoms, dental pain, feelings of gastrointestinal pressure, gastritis, gastroenteritis, hypersalivation, abdominal distention, oral itching and irritation, salivary gland swelling and swallowing disorders.

Hematological Disorders: Rare was anemia.

Musculoskeletal: Frequent was myalgia. Infrequent was muscle cramps. Rare were tetany; muscle atrophy, weakness and tiredness; arthralgia and articular rheumatitis; acquired musculoskeletal deformity; muscle stiffness, tightness and rigidity; and musculoskeletal inflammation.

Neurological: Frequent were phonophobia and photophobia. Infrequent were confusion, depression, difficulty concentrating, disturbance of smell, dysarthria, euphoria, facial pain, heat sensitivity, incoordination, lacrimation, monoplegia, sleep disturbance, shivering, syncope and tremor. Rare were aggressiveness, apathy, bradylogia, cluster headache, convulsions, decreased appetite, drug abuse, dystonic reaction, facial paralysis, hallucinations, hunger, hyperesthesia, hysteria, increased alertness, memory disturbance, neuralgia, paralysis, personality change, phobia, radiculopathy, rigidity, suicide, twitching, agitation, anxiety, depressive disorders, detachment, motor dysfunction, neurotic disorders, psychomotor disorders, taste disturbances and raised intracranial pressure.

Respiratory: Frequent was dyspnea. Infrequent was asthma. Rare were hiccoughs, breathing disorders, cough and bronchitis.

Skin: Frequent was sweating. Infrequent were erythema, pruritus, rash and skin tenderness. Rare were dry/scaly skin, tightness of skin, wrinkling of skin, eczema, seborrheic dermatitis and skin nodules.

Breasts: Infrequent was tenderness. Rare were nipple discharge; breast swelling; cysts, lumps and masses of breasts; and primary malignant breast neoplasm.

Urogenital: Infrequent were dysmenorrhea, increased urination and intermenstrual bleeding. Rare were abortion and hematuria, urinary frequency, bladder inflammation, micturition disorders, urethritis, urinary infections, menstruation symptoms, abnormal menstrual cycle, inflammation of fallopian tubes and menstrual cycle symptoms.

Miscellaneous: Frequent was hypersensitivity. Infrequent were fever, fluid retention and overdose. Rare were edema, hematoma, lymphadenopathy, speech disturbance, voice disturbances, contusions.

Other Events Observed in the Clinical Development of Sumatriptan Succinate

The following adverse events occurred in clinical trials with sumatriptan succinate injection and sumatriptan nasal spray. Because the reports include events observed in open and uncontrolled studies, the role of sumatriptan 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.

Atypical Sensations: Feeling strange, prickling sensation, tingling and hot sensation

Cardiovascular: Abdominal aortic aneurysm, abnormal pulse, flushing, phlebitis, Raynaud syndrome and 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)

Chest Symptoms: Chest discomfort

Endocrine and Metabolic: Dehydration

Ear, Nose and Throat: Disorder/discomfort nasal cavity and sinuses, ear infection, Meniere disease and throat discomfort

Eye: Vision alterations

Gastrointestinal: Abdominal discomfort, colitis, disturbance of liver function tests, flatulence/eructation, gallstones, intestinal obstruction, pancreatitis and retching

Injection Site Reaction: Miscellaneous: Difficulty in walking, hypersensitivity to various agents, jaw discomfort, miscellaneous laboratory abnormalities, “serotonin agonist effect,” swelling of the extremities and swelling of the face

Mouth and Teeth: Disorder of mouth and tongue (e.g., burning of tongue, numbness of tongue, dry mouth)

Musculosketal: Arthritis, backache, intervertebral disc disorder, neck pain/stiffness, need to flex calf muscles and various joint disturbances (pain, stiffness, swelling, ache)

Neurological: Bad/unusual taste, chills, diplegia, disturbance of emotions, sedation, globus hystericus, intoxication, myoclonia, neoplasm of pituitary, relaxation, sensation of lightness, simultaneous hot and cold sensations, stinging sensations, stress, tickling sensations, transient hemiplegia and yawning

Respiratory: Influenza and diseases of the lower respiratory tract and lower respiratory tract infection

Skin: Skin eruption, herpes and peeling of the skin

Urogenital: Disorder of breasts, endometriosis and renal calculus. 

Post-Marketing 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 post-marketing experience, frequency of events and the role of sumatriptan 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]), photosensitivity

Urogenital: Acute renal failure.

DRUG ABUSE AND DEPENDENCE

One clinical study with sumatriptan succinate injection 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 = 670) have received single oral doses of 140 mg to 300 mg without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 mg to 400 mg without serious adverse events.

Overdose in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation and lacrimation. The elimination half-life of sumatriptan is approximately 2.5 hours (see CLINICAL PHARMACOLOGY), and therefore monitoring of patients after overdose with sumatriptan succinate tablets should continue for at least 12 hours or while symptoms or signs persist.

It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

DOSAGE AND ADMINISTRATION

In controlled clinical trials, single doses of 25 mg, 50 mg or 100 mg of sumatriptan succinate tablets were effective for the acute treatment of migraine in adults. There is evidence that doses of 50 mg and 100 mg may provide a greater effect than 25 mg (see CLINICAL TRIALS). There is also evidence that doses of 100 mg do not provide a greater effect than 50 mg. Individuals may vary in response to doses of sumatriptan succinate tablets. The choice of dose should therefore be made on an individual basis, weighing the possible benefit of a higher dose with the potential for a greater risk of adverse events.

If the headache returns or the patient has a partial response to the initial dose, the dose may be repeated after 2 hours, not to exceed a total daily dose of 200 mg. If a headache returns following an initial treatment with sumatriptan succinate injection, additional single sumatriptan succinate tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses. The safety of treating an average of more than four headaches in a 30-day period has not been established.

Because of the potential of MAO-A inhibitors to cause unpredictable elevations in the bioavailability of oral sumatriptan, their combined use is contraindicated (see CONTRAINDICATIONS).

Hepatic disease/functional impairment may also cause unpredictable elevations in the bioavailability of orally administered sumatriptan. Consequently, if treatment is deemed advisable in the presence of liver disease, the maximum single dose should in general not exceed 50 mg (see CLINICAL PHARMACOLOGY for the basis of this recommendation).

HOW SUPPLIED

Sumatriptan Succinate Tablets are available as 25 mg, 50 mg or 100 mg of sumatriptan (base) as the succinate.

The 25 mg tablets are white film-coated, round tablets debossed with M on one side of the tablet and S4 on the other side. They are available as follows:

NDC 0378-5630-59
bottles of 9 tablets

NDC 0378-5630-01
bottles of 100 tablets

The 50 mg tablets are white film-coated, round tablets debossed with M over S7 on one side of the tablet and blank on the other side. They are available as follows:

NDC 0378-5631-59
bottles of 9 tablets

NDC 0378-5631-01
bottles of 100 tablets

The 100 mg tablets are white film-coated, round tablets debossed with M over S12 on one side of the tablets and blank on the other side. They are available as follows:

NDC 0378-5632-59
bottles of 9 tablets

NDC 0378-5632-01
bottles of 100 tablets

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

PHARMACIST: Dispense a Patient Information Leaflet with each prescription.

ANIMAL TOXICOLOGY

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 one 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. There is evidence of alterations in corneal appearance on the first day of intranasal dosing to dogs. Changes were noted at the lowest dose tested, which was approximately one-half the maximum single human oral dose of 100 mg on a mg/m2 basis.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

MAY 2009
SUMA:R1p

PATIENT INFORMATION
SUMATRIPTAN SUCCINATE TABLETS

Read this leaflet carefully before you start to take sumatriptan succinate tablets. Keep the leaflet for reference because it gives you a summary of important information about sumatriptan succinate tablets.

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 sumatriptan succinate tablets. Ask your healthcare provider for more information or advice.

What are sumatriptan succinate tablets?

Sumatriptan succinate tablets are a kind of medicine called a triptan. You should take it only if you have a prescription.

Sumatriptan succinate tablets are used to relieve your migraine. They are not used to prevent attacks or reduce the number of attacks you have. Use sumatriptan succinate tablets only to treat an actual migraine attack.

The decision to use sumatriptan succinate tablets is one that you and your healthcare provider should make together, based on your personal needs and health.

Talk with your healthcare provider before taking sumatriptan succinate tablets

  1. Risk factors for heart disease to tell your healthcare provider:
    Tell your healthcare provider if you have risk factors for heart disease such as:
         ▪ high blood pressure
         ▪ high cholesterol
         ▪ being overweight
         ▪ diabetes
         ▪ smoking
         ▪ strong family history of heart disease
         ▪ you are postmenopausal
         ▪ 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 sumatriptan is right for you.

    Although most of the people who have taken sumatriptan 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 sumatriptan succinate tablets. Usually, serious problems happened in people with known heart disease. It was not clear whether sumatriptan had anything to do with these deaths.

  2. Important questions to ask yourself before you take sumatriptan succinate tablets:
    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 take sumatriptan succinate tablets.
         ▪ Are you pregnant? Do you think you might be pregnant? Are you trying to become pregnant? Are you not using adequate contraception? Are you breast-feeding?
         ▪ 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 (see list above)?
         ▪ Have you had a stroke, a mini-stroke (also called a transient ischemic attack or TIA), 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 triptans? Are you taking any medicines containing ergotamine, dihydroergotamine or methysergide?
         ▪ Are you taking any medicine for depression or other health problems such as a monoamine oxidase inhibitor, selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI)? Common SSRIs are citalopram HBr (CELEXA®†), escitalopram oxalate (LEXAPRO®†), paroxetine (PAXIL®†), fluoxetine (PROZAC®†/SARAFEM®†), olanzapine/fluoxetine (SYMBYAX®†), sertraline (ZOLOFT®†) and fluvoxamine. Common SNRIs are duloxetine (CYMBALTA®†) and venlafaxine (EFFEXOR®†).
         ▪ 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 sumatriptan succinate tablets

  1. The use of sumatriptan succinate tablets during pregnancy:

    Do not take sumatriptan succinate tablets 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.

  2. How to take sumatriptan succinate tablets:

    For adults, the usual dose is a single tablet swallowed whole with water or other liquids. Do not split tablets. If your symptoms of migraine come back or if you have a partial response to the first dose, you can take a second tablet 2 hours after the first tablet, but not sooner.

    For any attack where you have no response to the first tablet, do not take a second tablet without first talking to your healthcare provider. Do not take more than a total of 200 mg of sumatriptan succinate tablets in any 24-hour period. The safety of treating an average of more than four headaches in a 30-day period has not been established.

  3. 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 right away.

  4. How to store your medicine:

    Keep your medicine in a safe place where children cannot reach it. It may be harmful to children.

    Do not take tablets out of the packaging until you are ready to take them. Do not store the tablets in any other container.

    Store your medicine away from heat and light. Store at 20° to 25°C (68° to 77°F).

    The expiration date of your medicine is printed on the packaging. If your medicine has expired, throw it away.

    If your healthcare provider decides to stop your treatment, do not keep any leftover medicine unless your healthcare provider tells you to.

Some possible side effects of sumatriptan succinate tablets

  • Some patients feel pain or tightness in the chest or throat when using sumatriptan succinate tablets. If this happens to you, tell your healthcare provider before taking any more sumatriptan succinate tablets. If the chest pain, tightness or pressure 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 after you take sumatriptan succinate tablets.
  • Some people may have a reaction called serotonin syndrome when they take certain kinds of medicines for depression called SSRIs or SNRIs while they are taking sumatriptan succinate tablets. Symptoms may include confusion, hallucinations, fast heartbeat, feeling faint, fever, sweating, muscle spasm, difficulty walking and/or diarrhea. Call your healthcare provider right away if you have any of these symptoms after taking sumatriptan succinate tablets.
  • 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 sumatriptan succinate tablets 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 taking sumatriptan succinate tablets. 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.
  • 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.

The brand names mentioned in this Medication Guide are registered trademarks of their respective manufacturers.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

MAY 2009
PL:SUMA:R1

PRINCIPAL DISPLAY PANEL - 25 mg

NDC 0378-5630-59

SUMATRIPTAN
SUCCINATE
TABLETS
25 mg*

PHARMACIST: PLEASE DISPENSE WITH
ATTACHED PATIENT INFORMATION LEAFLET.

9 TABLETS (Rx only)

*Each film-coated tablet
contains sumatriptan
succinate, USP equivalent
to 25 mg of sumatriptan.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying
prescribing information.

Swallow tablet whole with water.

Do not split tablets.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

RM5630CL

Sumatriptan 25 mg tablets in bottles of 9

PRINCIPAL DISPLAY PANEL - 25 mg

NDC 0378-5630-01

SUMATRIPTAN
SUCCINATE
TABLETS
25 mg*

PHARMACIST: PLEASE DISPENSE WITH
ATTACHED PATIENT INFORMATION LEAFLET.

100 TABLETS (Rx only)

*Each film-coated tablet
contains sumatriptan
succinate, USP equivalent
to 25 mg of sumatriptan.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying
prescribing information.

Swallow tablet whole with water.

Do not split tablets.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

RM5630A

Sumatriptan 25 mg tablets in bottles of 100

PRINCIPAL DISPLAY PANEL - 50 mg

NDC 0378-5631-59

SUMATRIPTAN
SUCCINATE
TABLETS
50 mg*

PHARMACIST: PLEASE DISPENSE WITH
ATTACHED PATIENT INFORMATION LEAFLET.

9 TABLETS (Rx only)

*Each film-coated tablet
contains sumatriptan
succinate, USP equivalent
to 50 mg of sumatriptan.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying
prescribing information.

Swallow tablet whole with water.

Do not split tablets.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

RM5631CL

Sumatriptan 50 mg tablets in bottles of 9

PRINCIPAL DISPLAY PANEL - 50 mg

NDC 0378-5631-01

SUMATRIPTAN
SUCCINATE
TABLETS
50 mg*

PHARMACIST: PLEASE DISPENSE WITH
ATTACHED PATIENT INFORMATION LEAFLET.

100 TABLETS (Rx only)

*Each film-coated tablet
contains sumatriptan
succinate, USP equivalent
to 50 mg of sumatriptan.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying
prescribing information.

Swallow tablet whole with water.

Do not split tablets.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

RM5631A

Sumatriptan 50 mg tablets in bottles of 100

PRINCIPAL DISPLAY PANEL - 100 mg

NDC 0378-5632-59

SUMATRIPTAN
SUCCINATE
TABLETS
100 mg*

PHARMACIST: PLEASE DISPENSE WITH
ATTACHED PATIENT INFORMATION LEAFLET.

9 TABLETS (Rx only)

*Each film-coated tablet
contains sumatriptan
succinate, USP equivalent
to 100 mg of sumatriptan.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying
prescribing information.

Swallow tablet whole with water.

Do not split tablets.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

RM5632CL

Sumatriptan 100 mg tablets in bottles of 9

PRINCIPAL DISPLAY PANEL - 100 mg

NDC 0378-5632-01

SUMATRIPTAN
SUCCINATE
TABLETS
100 mg*

PHARMACIST: PLEASE DISPENSE WITH
ATTACHED PATIENT INFORMATION LEAFLET.

100 TABLETS (Rx only)

*Each film-coated tablet
contains sumatriptan
succinate, USP equivalent
to 100 mg of sumatriptan.

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying
prescribing information.

Swallow tablet whole with water.

Do not split tablets.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

RM5632A

Sumatriptan 100 mg tablets in bottles of 100


SUMATRIPTAN SUCCINATE 
sumatriptan succinate tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-5630
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SUMATRIPTAN SUCCINATE (SUMATRIPTAN) SUMATRIPTAN 25 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
CROSCARMELLOSE SODIUM  
HYPROMELLOSE  
LACTOSE MONOHYDRATE  
MAGNESIUM STEARATE  
CELLULOSE, MICROCRYSTALLINE  
POLYDEXTROSE  
POLYETHYLENE GLYCOL  
POVIDONE  
SODIUM LAURYL SULFATE  
TITANIUM DIOXIDE  
TRIACETIN  
Product Characteristics
Color WHITE Score no score
Shape ROUND Size 6mm
Flavor Imprint Code M;S4
Contains     
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0378-5630-59 9 TABLET, FILM COATED ( TABLET) in 1 BOTTLE, PLASTIC None
2 NDC:0378-5630-01 100 TABLET, FILM COATED ( TABLET) in 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077744 08/24/2009

SUMATRIPTAN SUCCINATE 
sumatriptan succinate tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-5631
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SUMATRIPTAN SUCCINATE (SUMATRIPTAN) SUMATRIPTAN 50 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
CROSCARMELLOSE SODIUM  
HYPROMELLOSE  
LACTOSE MONOHYDRATE  
MAGNESIUM STEARATE  
CELLULOSE, MICROCRYSTALLINE  
POLYDEXTROSE  
POLYETHYLENE GLYCOL  
POVIDONE  
SODIUM LAURYL SULFATE  
TITANIUM DIOXIDE  
TRIACETIN  
Product Characteristics
Color WHITE Score no score
Shape ROUND Size 8mm
Flavor Imprint Code M;S7
Contains     
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0378-5631-59 9 TABLET, FILM COATED ( TABLET) in 1 BOTTLE, PLASTIC None
2 NDC:0378-5631-01 100 TABLET, FILM COATED ( TABLET) in 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077744 08/24/2009

SUMATRIPTAN SUCCINATE 
sumatriptan succinate tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-5632
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SUMATRIPTAN SUCCINATE (SUMATRIPTAN) SUMATRIPTAN 100 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
CROSCARMELLOSE SODIUM  
HYPROMELLOSE  
LACTOSE MONOHYDRATE  
MAGNESIUM STEARATE  
CELLULOSE, MICROCRYSTALLINE  
POLYDEXTROSE  
POLYETHYLENE GLYCOL  
POVIDONE  
SODIUM LAURYL SULFATE  
TITANIUM DIOXIDE  
TRIACETIN  
Product Characteristics
Color WHITE Score no score
Shape ROUND Size 10mm
Flavor Imprint Code M;S12
Contains     
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0378-5632-59 9 TABLET, FILM COATED ( TABLET) in 1 BOTTLE, PLASTIC None
2 NDC:0378-5632-01 100 TABLET, FILM COATED ( TABLET) in 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077744 08/24/2009

Labeler - Mylan Pharmaceuticals Inc. (059295980)

Revised: 05/2009 Mylan Pharmaceuticals Inc.



Source: http://dailymed.nlm.nih.gov
Reproduced with permission of U.S. National Library of Medicine


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