Sumatriptan Succinate
FDA Label NDC 54868-5978

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.

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 Succinate and another 5-HT₁ agonist.

Sumatriptan Succinate Tablets are contraindicated in patients with hypersensitivity to sumatriptan or any of their components.

Sumatriptan Succinate Tablets are contraindicated in patients with severe hepatic impairment.

Sumatriptan Succinate Tablets should only be used where a clear diagnosis of migraine headache has been established.

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 Succinate 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 an electrocardiogram (ECG) during the interval immediately following the first dose 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.

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 injection or 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.

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 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.

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.

Serious cardiovascular events, some resulting in death, have been reported in association with the use of sumatriptan injection or tablets. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively the proportion of the reported cases that were actually caused by sumatriptan or to reliably assess causation in individual cases. On clinical grounds, the longer the latency between the administration of sumatriptan and the onset of the clinical event, the less likely the association is to be causative. Accordingly, interest has focused on events beginning within 1 hour of the administration of sumatriptan.

Cardiac events that have been observed to have onset within 1 hour of sumatriptan administration include: coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation, cardiac arrest, and death.

Some of these events occurred in patients who had no findings of CAD and appear to represent consequences of coronary artery vasospasm. However, among domestic reports of serious cardiac events within 1 hour of sumatriptan administration, almost all of the patients had risk factors predictive of CAD and the presence of significant underlying CAD was established in most cases (see CONTRAINDICATIONS).

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with oral or subcutaneous sumatriptan, and some have resulted in fatalities. The relationship of sumatriptan to these events is uncertain. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. It should also be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., cerebrovascular accident, transient ischemic attack).

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.

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).

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.

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 and an MAO-A inhibitor is contraindicated (see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS).

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).

Chest discomfort and jaw or neck tightness have been reported following use of sumatriptan 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 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.

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.

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).

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.

No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment with sumatriptan.

Cases of life-threatening serotonin syndrome have been reported during combined use of SSRIs or SNRIs and triptans (see WARNINGS).

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).

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).

Sumatriptan is not known to interfere with commonly employed clinical laboratory tests.

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.

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.

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 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.

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 2.0 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 12.5 mg/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.

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.

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 1,000 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.

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 Sumatriptan Succinate Tablets.

Safety and effectiveness of sumatriptan 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 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 with 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.

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).

Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan 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, 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).

Table 2 lists adverse events that occurred in placebo-controlled clinical trials in patients who took at least 1 dose of study drug. Only events that occurred at a frequency of 2% or more in any group treated with sumatriptan 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.

^*Events that occurred at a frequency of 2% or more in the group treated with sumatriptan tablets and that occurred more frequently in that group than the placebo group.

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

Sumatriptan 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.

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 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 tablets (25, 50, or 100 mg) and reported an event divided by the total number of patients (N = 6,348) exposed to sumatriptan 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.

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

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.

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).

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.

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.

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.

Rare was anemia.

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.

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.

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

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.

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

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.

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

The following adverse events occurred in clinical trials with sumatriptan injection and 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.

Feeling strange, prickling sensation, tingling, and hot sensation.

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 discomfort.

Dehydration.

Disorder/discomfort nasal cavity and sinuses, ear infection, Meniere disease, and throat discomfort.

Vision alterations.

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

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

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

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

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.

Influenza and diseases of the lower respiratory tract and lower respiratory tract infection.

Skin eruption, herpes, and peeling of the skin.

Disorder of breasts, endometriosis, and renal calculus.

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 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.

Hemolytic anemia, pancytopenia, thrombocytopenia.

Atrial fibrillation, cardiomyopathy, colonic ischemia (see WARNINGS), Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis.

Deafness.

Ischemic optic neuropathy, retinal artery occlusion, retinal vein thrombosis, loss of vision.

Ischemic colitis with rectal bleeding (see WARNINGS), xerostomia.

Elevated liver function tests.

Central nervous system vasculitis, cerebrovascular accident, dysphasia, serotonin syndrome, subarachnoid hemorrhage.

Angioneurotic edema, cyanosis, death (see WARNINGS), temporal arteritis.

Panic disorder.

Bronchospasm in patients with and without a history of asthma.

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.

Acute renal failure.

One clinical study with sumatriptan 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.

Patients (N = 670) have received single oral doses of 140 to 300 mg without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 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.

In controlled clinical trials, single doses of 25, 50, or 100 mg of sumatriptan tablets were effective for the acute treatment of migraine in adults. There is evidence that doses of 50 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 4 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).

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

Sumatriptan Succinate Tablets, 50 mg are white, triangular-shaped, film-coated tablets debossed with “S” on one side and “50” on the other in blister packs of 9 tablets (NDC 54868-6023-0).

Sumatriptan Succinate Tablets, 100 mg, are white, triangular-shaped, film-coated tablets debossed with “S” on one side and “100” on the other in blister packs of 9 tablets (NDC 54868-5978-0).

Store between 36° and 86°F (2° and 30°C).

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. 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.

The following wording is contained in a separate leaflet provided for patients.

Information for the Patient

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

• 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 Succinate Tablets are 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. Usually, serious problems happened in people with known heart disease. It was not clear whether sumatriptan had anything to do with these deaths.

  • 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 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 (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

    • 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.

    • 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 4 headaches in a 30-day period has not been established.

    • 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.

    • 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. Do not store at temperatures above 86°F (30°C) or below 36°F (2°C).

      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.

    November 2008 SMT-DR:1PIL

    The following are registered trademarks of their respective owners: CELEXA, LEXAPRO/Forest Laboratories, Inc.; PAXIL/GlaxoSmithKline; PROZAC, SYMBYAX, CYMBALTA/Eli Lilly and Company; SARAFEM/Warner Chilcott (US), Inc.; ZOLOFT/Pfizer Inc.; EFFEXOR/Wyeth Corporation.

    Manufactured by Penn Labs

    (a GlaxoSmithKline company)

    for Dr. Reddy’s Laboratories Inc.

    Bridgewater, NJ 08807

    November 2008 SMT-DR:1PI

    
    

    
    

    Relabeling of "Additional Barcode" by:
    Physicians Total Care, Inc.
    Tulsa, OK      74146
    

Sumatriptan Succinate Tablets

50 mg

R_x only

9 Tablets

Each tablet contains sumatriptan succinate equivalent to 25 mg of sumatriptan.

Do not use if package is torn or broken or if you receive fewer tablets than your doctor prescribed.

See prescribing information for dosage information.

Store between 36^o and 86^oF (2^o to 30^oC).

Sumatriptan Succinate Tablets

100 mg

R_x only

9 Tablets

Each tablet contains sumatriptan succinate equivalent to 25 mg of sumatriptan.

Do not use if package is torn or broken or if you receive fewer tablets than your doctor prescribed.

See prescribing information for dosage information.

Store between 36^o and 86^oF (2^o to 30^oC).