Sumatriptan Succinate (sumatriptan succinate 50 mg) Dailymed

1 Indications And Usage

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

Limitations of Use:

• Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine attack treated with sumatriptan, reconsider the diagnosis of migraine before sumatriptan tablets are administered to treat any subsequent attacks.

• Sumatriptan tablets are not indicated for the prevention of migraine attacks.

• Safety and effectiveness of sumatriptan tablets have not been established for cluster headache.


Sumatriptan is a serotonin (5-HT_1B/1D) receptor agonist (triptan) indicated for acute treatment of migraine with or without aura in adults. ( 1)

Limitations of Use:

• Use only if a clear diagnosis of migraine headache has been established. ( 1 )
• Not indicated for the prophylactic therapy of migraine attacks. ( 1 )
• Not indicated for the treatment of cluster headache. ( 1 )

2 Dosage And Administration

• Single dose of 25 mg, 50 mg, or 100 mg tablet.( 2.1 )
• A second dose should only be considered if some response to the first dose was observed. Separate doses by at least 2 hours. ( 2.1 )
• Maximum dose in a 24-hour period: 200 mg. ( 2.1 )
• Maximum single dose should not exceed 50 mg in patients with mild to moderate hepatic impairment. ( 2.2 )

2.1

The recommended dose of sumatriptan tablets are 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25-mg dose, but doses of 100 mg may not provide a greater effect than the 50-mg dose. Higher doses may have a greater risk of adverse reactions [see Clinical Studies (14 )].  

If the migraine has not resolved by 2 hours after taking sumatriptan tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24-hour period.  

Use after sumatriptan injection:

If the migraine returns following an initial treatment with sumatriptan injection, additional single sumatriptan 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 24 been established.

2.2 Dosing in Patients with Hepatic Impairment

If treatment is deemed advisable in the presence of mild to moderate hepatic impairment, the maximum single dose should not exceed 50 mg [see Use in Specific Populations ( 8.6 ) and  Clinical Pharmacology ( 12.3 )].

• Myocardial ischemia/infarction and Prinzmetal’s angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. ( 5.1 )
• Arrhythmias: Discontinue sumatriptan if occurs. ( 5.2 )
• Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for coronary artery disease in patients at high risk. ( 5.3 )
• Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue sumatriptan  if occurs. ( 5.4 )
• Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue sumatriptan if occurs. ( 5.5 )
• Medication overuse headache: Detoxification may be necessary. ( 5.6 )
• Serotonin syndrome: Discontinue sumatriptan if occurs. ( 5.7 )
• Seizures: Use with caution in patients with epilepsy or a lowered seizure threshold. ( 5.10 )

5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetals Angina

The use of sumatriptan tablets are contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of sumatriptan tablets.  Some of these reactions occurred in patients without known CAD. Sumatriptan  tablets may cause coronary artery vasospasm (Prinzmetal’s angina), even in patients without a history of CAD.  

Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan  tablets. If there is evidence of CAD or coronary artery vasospasm, sumatriptan tablets are contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of sumatriptan tablets in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of sumatriptan tablets. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of sumatriptan tablets.

5.2 Arrhythmias

Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT₁ agonists. Discontinue sumatriptan tablets if these disturbances occur. Sumatriptan tablets are contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure

Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan tablets and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of sumatriptan tablets are contraindicated in patients with CAD and those with Prinzmetal’s variant angina.

5.4 Cerebrovascular Events

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT₁ agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT₁ agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue sumatriptan tablets if a cerebrovascular event occurs.  

Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, exclude other potentially serious neurological conditions.  Sumatriptan tablets are contraindicated in patients with a history of stroke or TIA.

5.5 Other Vasospasm Reactions

Sumatriptan tablets may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud’s syndrome. In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT₁ agonist, rule out a vasospastic reaction before receiving additional sumatriptan tablets.  

Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT₁ agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT₁ agonists have not been clearly established.

5.6 Medication Overuse Headache

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.  

5.7 Serotonin Syndrome

Serotonin syndrome may occur with sumatriptan tablets, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions ( 7.4 )]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue sumatriptan tablets if serotonin syndrome is suspected.

5.8 Increase in Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT₁ agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with sumatriptan. Sumatriptan tablets are contraindicated in patients with uncontrolled hypertension.

5.9 Anaphylactic/Anaphylactoid Reactions

Anaphylactic/anaphylactoid reactions have occurred in patients receiving sumatriptan. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. Sumatriptan  tablets are contraindicated in patients with a history of hypersensitivity reaction to sumatriptan.

5.10 Seizures

Seizures have been reported following administration of sumatriptan. Some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures. There are also reports in patients where no such predisposing factors are apparent. Sumatriptan  tablets should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

6 Adverse Reactions

The following adverse reactions are discussed in more detail in other sections of the prescribing information:

• Myocardial ischemia, myocardial infarction, and Prinzmetal’s angina [see Warnings and  Precautions ( 5.1 )]

• Arrhythmias [see Warnings and Precautions ( 5.2 )]

• Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions ( 5.3 )] 

• Cerebrovascular events [see Warnings and Precautions ( 5.4 )]

• Other vasospasm reactions [see Warnings and Precautions ( 5.5 )]

• Medication overuse headache [see Warnings and Precautions ( 5.6 )]

• Serotonin syndrome [see Warnings and Precautions ( 5.7 )]

• Increase in blood pressure [see Warnings and Precautions ( 5.8 )]

• Hypersensitivity reactions [see Contraindications (4 ), Warnings and Precautions ( 5.9 )]

• Seizures [see Warnings and Precautions ( 5.10 )]  


Most common adverse reactions (≥2% and >placebo) were paresthesia, warm/cold sensation, chest pain/tightness/pressure and/or heaviness, neck/throat/jaw pain/tightness/pressure, other sensations of pain/pressure/tightness/heaviness, vertigo, and malaise/fatigue. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc. at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.  

Table 1 uls adverse reactions that occurred in placebo-controlled clinical trials in patients who took at least 1 dose of study drug. Only treatment-emergent adverse reactions that occurred at a frequency of 2% or more in any group treated with sumatriptan  tablets and that occurred at a frequency greater than the placebo group are included in Table 1.

 Table 1. Adverse Reactions Reported by at Least 2% of Patients Treated with Sumatriptan Tablets  and at a Greater Frequency than Placebo

	Percent of Patients Reporting
Adverse Reaction	Sumatriptan  Tablets 25 mg (n = 417)	Sumatriptan  Tablets 50 mg (n = 771)	Sumatriptan  Tablets 100 mg (n = 437)	Placebo (n = 309)
Atypical sensations	5	6	6	4
Paresthesia (all types)	3	5	3	2
Sensation warm/cold	3	2	3	2
Pain and other pressure sensations Chest-pain/tightness/ pressure and/or heaviness Neck/throat/jaw-pain/ tightness/pressure Pain-location specified Other-pressure/tightness/ heaviness	6  1  <1  2  1	6  2  2  1  1	8  2  3 1 3	4 1  <1  1  2
Neurological Vertigo	<1	<1	2	<1
Other Malaise/fatigue	2	2	3	<1

The incidence of adverse reactions 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 reactions.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of sumatriptan  tablets, sumatriptan nasal spray, and sumatriptan  injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to sumatriptan or a combination of these factors.

Cardiovascular:

Hypotension, palpitations.

Neurological:

Dystonia, tremor.

7 Drug Interactions

7.1 Ergot-Containing Drugs

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan tablets within 24 hours of each other is contraindicated.

7.2 Monoamine Oxidase-A Inhibitors

MAO-A inhibitors increase systemic exposure by 7-fold. Therefore, the use of sumatriptan  tablets in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology ( 12.3 )].

7.3 Other 5-HT Agonists

Because their vasospastic effects may be additive, co administration of sumatriptan  tablets and other 5-HT₁ agonists (e.g., triptans) within 24 hours of each other is contraindicated.

7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome

Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions ( 5.7 )].

8 Use In Specific Populations

Pregnancy: Based on animal data, may cause fetal harm. (8.1)

8.1 Pregnancy

Risk Summary

Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see Data). In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal (see Data).  

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine.  

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk: Several studies have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy.  

Data

Human Data:  

The Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study, collected data for sumatriptan from January 1996 to September 2012. The Registry documented outcomes of 626 infants and fetuses exposed to sumatriptan during pregnancy (528 with earliest exposure during the first trimester, 78 during the second trimester, 16 during the third trimester, and 4 unknown). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95% CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95% CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at least a 1.73-to 1.91-fold increase in the rate of major malformations. The number of exposed pregnancy outcomes accumulated during the registry was insufficient to support definitive conclusions about overall malformation risk or for making comparisons of the frequencies of specific birth defects. Of the 20 infants with reported birth defects after exposure to sumatriptan in the first trimester, 4 infants had ventricular septal defects, including one infant who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric stenosis. No other birth defect was reported for more than 2 infants in this group.  

In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 2,257 births with first-trimester exposure to sumatriptan, 107 infants were born with malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for sumatriptan before pregnancy only, compared with a population control group. Of the 415 women who redeemed prescriptions for sumatriptan during the first trimester, 15 had infants with major congenital malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20 had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to 2.88]), each compared with the population comparison group. Additional smaller observational studies evaluating use of sumatriptan during pregnancy have not suggested an increased risk of teratogenicity.  

Animal Data:

Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day, or approximately 3 times the maximum recommended human dose (MRHD) of 200 mg/day on a mg/m² basis. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 (approximately 2 times the MRHD on a mg/m² basis) and 0.75 mg/kg/day, respectively.  

Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day, or approximately 2 times the MRHD on a mg/m² basis. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day, or approximately 3 times the MRHD on a mg/m² basis. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day, or approximately 5 times the MRHD on a mg/m² basis.

8.2 Lactation

Risk Summary

Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There is no information regarding sumatriptan concentrations in milk from lactating women following administration of sumatriptan tablets. There are no data on the effects of sumatriptan on the breastfed infant or the effects of sumatriptan on milk production.  

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sumatriptan tablets and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition.  

Clinical Considerations

Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with sumatriptan tablets.  

Data

Following subcutaneous administration of a 6 mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Sumatriptan tablets are not recommended for use in patients younger than 18 years of age.  

Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 adolescent migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.  

Five controlled clinical trials (2 single-attack trials, 3 multiple-attack trials) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 adolescent migraineurs. These trials did not establish the efficacy of oral sumatriptan compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose-and age-dependent, with younger patients reporting reactions more commonly than older adolescents.  

Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions 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. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available.

8.5 Geriatric Use

Clinical trials of sumatriptan tablets did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. 

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan tablets [see Warnings and Precautions ( 5.1 )].

8.6 Hepatic Impairment

The maximum single dose in patients with mild to moderate hepatic impairment should not exceed 50 mg. Sumatriptan tablets are contraindicated in patients with severe hepatic impairment [see Clinical Pharmacology ( 12.3 )].