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 and Naproxen Sodium Tablets, reconsider the diagnosis of migraine before Sumatriptan and Naproxen Sodium Tablets is administered to treat any subsequent attacks.
• Sumatriptan and Naproxen Sodium Tablets is not indicated for the prevention of migraine attacks.
• Safety and effectiveness of Sumatriptan and Naproxen Sodium Tablets have not been established for cluster headache.

2.1 Dosage in Adults

The recommended dosage for adults is 1 tablet of Sumatriptan and Naproxen Sodium Tablets 85/500 mg. Sumatriptan and Naproxen Sodium Tablets 85/500 mg contains a dose of sumatriptan higher than the lowest effective dose. The choice of the dose of sumatriptan, and of the use of a fixed combination such as in Sumatriptan and Naproxen Sodium Tablets 85/500 mg should be made on an individual basis, weighing the possible benefit of a higher dose of sumatriptan with the potential for a greater risk of adverse reactions.

The maximum recommended dosage in a 24-hour period is 2 tablets, taken at least 2 hours apart.

The safety of treating an average of more than 5 migraine headaches in adults in a 30-day period has not been established.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].

2.2 Dosage in Pediatric Patients 12 to 17 Years of Age

The recommended dosage for pediatric patients 12 to 17 years of age is 1 tablet of Sumatriptan and Naproxen Sodium Tablets 10/60 mg.

The maximum recommended dosage in a 24-hour period is 1 tablet of Sumatriptan and Naproxen Sodium Tablets 85/500 mg.

The safety of treating an average of more than 2 migraine headaches in pediatric patients in a 30-day period has not been established.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].

2.3 Dosing in Patients with Hepatic Impairment

Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with severe hepatic impairment [see Contraindications (4), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

In patients with mild to moderate hepatic impairment, the recommended dosage in a 24-hour period is 1 tablet of Sumatriptan and Naproxen Sodium Tablets 10/60 mg [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].

2.4 Administration Information

Sumatriptan and Naproxen Sodium Tablets may be administered with or without food. Tablets should not be split, crushed, or chewed.

5.1 Cardiovascular Thrombotic Events

The use of Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with ischemic or vasospastic coronary artery disease (CAD) and in the setting of coronary artery bypass graft (CABG) surgery due to increased risk of serious cardiovascular events with sumatriptan and NSAIDS [see Contraindications (4)].

5.2 Gastrointestinal Bleeding, Ulceration, and Perforation

NSAIDs, including naproxen, a component of Sumatriptan and Naproxen Sodium Tablets, cause serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only 1 in 5 patients who develop a serious upper gastrointestinal adverse event on NSAID therapy is symptomatic. Upper gastrointestinal ulcers, gross bleeding, or perforation caused by NSAIDs appear to occur in approximately 1% of patients treated daily for 3 to 6 months and in about 2% to 4% of patients treated for 1 year. However, even short-term therapy is not without risk.

Among 3,302 adult patients with migraine who received Sumatriptan and Naproxen Sodium Tablets in controlled and uncontrolled clinical trials, 1 patient experienced a recurrence of gastric ulcer after taking 8 doses over 3 weeks, and 1 patient developed a gastric ulcer after treating an average of 8 attacks per month over 7 months.

5.3 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 and Naproxen Sodium Tablets if these disturbances occur. Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

5.4 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 and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with CAD and those with Prinzmetal's variant angina.

5.5 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 and Naproxen Sodium 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 and Naproxen Sodium Tablets is contraindicated in patients with a history of stroke or TIA [see Contraindications (4)].

5.6 Other Vasospasm Reactions

Sumatriptan 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 and Naproxen Sodium 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.

5.7 Hepatotoxicity

Borderline elevations of 1 or more liver tests may occur in up to 15% of patients who take NSAIDs including naproxen, a component of Sumatriptan and Naproxen Sodium Tablets. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. Notable (3 times the upper limit of normal) elevations of SGPT (ALT) or SGOT (AST) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare, sometimes fatal cases of severe hepatic injury, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure have been reported with NSAIDs.

Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with severe hepatic impairment [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)]. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Sumatriptan and Naproxen Sodium Tablets. Sumatriptan and Naproxen Sodium Tablets should be discontinued if clinical signs and symptoms consistent with liver disease develop, if systemic manifestations occur (e.g., eosinophilia, rash), or if abnormal liver tests persist or worsen.

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flulike" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Sumatriptan and Naproxen Sodium Tablets immediately, and perform a clinical evaluation of the patient.

5.8 Hypertension

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 sumatriptan, a component of Sumatriptan and Naproxen Sodium Tablets. This occurrence has included patients without a history of hypertension.

NSAIDs, including naproxen, a component of Sumatriptan and Naproxen Sodium Tablets, can also lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cardiovascular events. Patients taking angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [see Drug Interactions (7)].

Monitor blood pressure in patients treated with Sumatriptan and Naproxen Sodium Tablets. Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].

5.9 Heart Failure and Edema

The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of naproxen may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see Drug Interactions (7)].

Avoid the use of Sumatriptan and Naproxen Sodium Tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Sumatriptan and Naproxen Sodium Tablets is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Since each Sumatriptan and Naproxen Sodium Tablets 85/500 mg tablet contains approximately 60 mg of sodium and each Sumatriptan and Naproxen Sodium Tablets 10/60 mg tablet contains approximately 20 mg of sodium, this should be considered in patients whose overall intake of sodium must be severely restricted.

5.10 Medication Overuse Headache

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or a 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.

5.11 Serotonin Syndrome

Serotonin syndrome may occur with Sumatriptan and Naproxen Sodium Tablets, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Contraindications (4) and Drug Interactions (7.1)]. 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 and Naproxen Sodium Tablets if serotonin syndrome is suspected.

5.12 Renal Toxicity and Hyperkalemia

5.13 Anaphylactic Reactions

Anaphylactic reactions may occur in patients without known prior exposure to either component of Sumatriptan and Naproxen Sodium Tablets. 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 although anaphylactic reactions with naproxen have occurred in patient without known hypersensitivity to naproxen or to patients with aspirin sensitive asthma [see Contraindications (4) and Warnings and Precautions (5.18)]. Sumatriptan and Naproxen Sodium Tablets should not be given to patients with the aspirin triad. This symptom complex typically occurs in patients with asthma who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs [see Contraindications (4)].

Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with a history of hypersensitivity reaction to sumatriptan, naproxen, or any other component of Sumatriptan and Naproxen Sodium Tablets. Naproxen has been associated with anaphylactic reactions in patients without known hypersensitivity to naproxen and in patients with aspirin-sensitive asthma [see Contraindications (4) and Warnings and Precautions (5.18)]. Seek emergency help if an anaphylactic reaction occurs.

5.14 Serious Skin Reactions

NSAID-containing products can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions and to discontinue the use of Sumatriptan and Naproxen Sodium Tablets at the first appearance of skin rash or any other sign of hypersensitivity. Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with previous serious skin reactions to NSAIDs [see Contraindications (4)].

5.15 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as Sumatriptan and Naproxen Sodium Tablets. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue Sumatriptan and Naproxen Sodium Tablets and evaluate the patient immediately.

5.16 Fetal Toxicity

5.17 Hematologic Toxicity

Anemia has occurred in patients receiving NSAIDs. This may be due to fluid retention, occult or gross gastrointestinal blood loss, or an incompletely described effect upon erythropoiesis. If a patient treated with Sumatriptan and Naproxen Sodium Tablets has signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including Sumatriptan and Naproxen Sodium Tablets, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see Drug Interactions (7)].

5.18 Exacerbation of Asthma Related to Aspirin Sensitivity

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma [see Contraindications (4)].

When Sumatriptan and Naproxen Sodium Tablets is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

5.19 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 and Naproxen Sodium Tablets should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

5.20 Masking of Inflammation and Fever

The pharmacological activity of Sumatriptan and Naproxen Sodium Tablets in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

5.21 Laboratory Monitoring

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [see Warnings and Precautions (5.2, 5.7, 5.12)].

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.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of NSAIDs, such as naproxen, which is a component of Sumatriptan and Naproxen Sodium Tablets. 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.

Skin and Appendages: exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE) [see Warnings and Precautions (5.14)].

7.1 Clinically Significant Drug Interactions with Sumatriptan and Naproxen Sodium Tablets

See Table 3 for clinically significant drug interactions with NSAIDs or Sumatriptan.

7.2 Drug/Laboratory Test Interactions

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

Safety and effectiveness of Sumatriptan and Naproxen Sodium Tablets in pediatric patients under 12 years of age have not been established.

The safety and efficacy of Sumatriptan and Naproxen Sodium Tablets for the acute treatment of migraine in pediatric patients 12 to 17 years of age was established in a double-blind, placebo-controlled trial [see Adverse Reactions (6.1) and Clinical Studies (14.2)].

8.5 Geriatric Use

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. Sumatriptan and Naproxen Sodium Tablets is not recommended for use in elderly patients who have decreased renal function, higher risk for unrecognized CAD, and increases in blood pressure that may be more pronounced in the elderly [see Warnings and Precautions (5.1, 5.2, 5.3, 5.8, 5.12) and Clinical Pharmacology (12.3)].

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 and Naproxen Sodium Tablets [see Warnings and Precautions (5.1)].

8.6 Renal Impairment

Sumatriptan and Naproxen Sodium Tablets is not recommended for use in patients with creatinine clearance less than 30 mL/min. Monitor the serum creatinine or creatinine clearance in patients with mild (CrCl = 60 to 89 mL/min) or moderate (CrCL = 30 to 59 mL/min) renal impairment, preexisting kidney disease, or dehydration [see Warnings and Precautions (5.12) and Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

Sumatriptan and Naproxen Sodium Tablets is contraindicated in patients with severe hepatic impairment. For patients with mild or moderate hepatic impairment, the Sumatriptan and Naproxen Sodium Tablets dose should be reduced. [see Contraindications (4), Warnings and Precautions (5.7), and Clinical Pharmacology (12.3)].

12.1 Mechanism of Action

Sumatriptan and Naproxen Sodium Tablets contains sumatriptan and naproxen.

Sumatriptan binds with high affinity to cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of neuropeptide release.

Sumatriptan and Naproxen Sodium Tablets has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of Sumatriptan and Naproxen Sodium Tablets, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Naproxen is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because naproxen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

12.2 Pharmacodynamics

In a healthy volunteer study, 10 days of concomitant administration of naproxen 220 mg once-daily with low-dose immediate-release aspirin (81 mg) showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane B2 inhibition at 24 hours following the day 10 dose [98.7% (aspirin alone) vs 93.1% (naproxen and aspirin)]. The interaction was observed even following discontinuation of naproxen on day 11 (while aspirin dose was continued) but normalized by day 13. In the same study, the interaction was greater when naproxen was administered 30 minutes prior to aspirin [98.7% vs 87.7%] and minimal when aspirin was administered 30 minutes prior to naproxen [98.7% vs 95.4%].

Following administration of naproxen 220 mg twice-daily with low-dose immediate–release aspirin (first naproxen dose given 30 minutes prior to aspirin), the interaction was minimal at 24 h following day 10 dose [98.7% vs 95.7%]. However, the interaction was more prominent after discontinuation of naproxen (washout) on day 11 [98.7% vs 84.3%] and did not normalize completely by day 13 [98.5% vs 90.7%] [see Drug Interactions (7.1)].

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14.1 Adults

The efficacy of Sumatriptan and Naproxen Sodium Tablets in the acute treatment of migraine with or without aura in adults was demonstrated in 2 randomized, double-blind, multicenter, parallel-group trials utilizing placebo and each individual active component of Sumatriptan and Naproxen Sodium Tablets 85/500 mg (sumatriptan and naproxen sodium) as comparison treatments (Study 1 and Study 2). Patients enrolled in these 2 trials were predominately female (87%) and white (88%), with a mean age of 40 years (range: 18 to 65 years). Patients were instructed to treat a migraine of moderate to severe pain with 1 tablet. No rescue medication was allowed within 2 hours postdose. Patients evaluated their headache pain 2 hours after taking 1 dose of study medication; headache relief was defined as a reduction in headache severity from moderate or severe pain to mild or no pain. Associated symptoms of nausea, photophobia, and phonophobia were also evaluated. Sustained pain free was defined as a reduction in headache severity from moderate or severe pain to no pain at 2 hours postdose without a return of mild, moderate, or severe pain and no use of rescue medication for 24 hours postdose. The results from Study 1 and 2 are summarized in Table 4. In both trials, the percentage of patients achieving headache pain relief 2 hours after treatment was significantly greater among patients receiving Sumatriptan and Naproxen Sodium Tablets 85/500 mg (65% and 57%) compared with those who received placebo (28% and 29%).

Further, the percentage of patients who remained pain free without use of other medications through 24 hours postdose was significantly greater among patients receiving a single dose of Sumatriptan and Naproxen Sodium Tablets 85/500 mg (25% and 23%) compared with those who received placebo (8% and 7%) or either sumatriptan (16% and 14%) or naproxen sodium (10%) alone.

The percentage of patients achieving initial headache pain relief within 2 hours following treatment with Sumatriptan and Naproxen Sodium Tablets 85/500 mg is shown in Figure 1.

Figure 1. Percentage of Adult Patients with Initial Headache Pain Relief within 2 Hours

Compared with placebo, there was a decreased incidence of photophobia, phonophobia, and nausea 2 hours after the administration of Sumatriptan and Naproxen Sodium Tablets 85/500 mg. The estimated probability of taking a rescue medication over the first 24 hours is shown in Figure 2.

Figure 2. Estimated Probability of Adults Taking a Rescue Medication over the 24 Hours following the First Dose1

Sumatriptan and Naproxen Sodium Tablets 85/500 mg was more effective than placebo regardless of the presence of aura; duration of headache prior to treatment; gender, age, or weight of the subject; or concomitant use of oral contraceptives or common migraine prophylactic drugs (e.g., beta-blockers, anti-epileptic drugs, tricyclic antidepressants).

1

Kaplan-Meier plot based on data obtained in the 2 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 rescue medication was allowed within 2 hours postdose.

14.2 Pediatric Patients 12 to 17 Years of Age

The efficacy of Sumatriptan and Naproxen Sodium Tablets in the acute treatment of migraine with or without aura in pediatric patients 12 to 17 years of age was demonstrated in a randomized, double-blind, multicenter, parallel-group, placebo-controlled, multicenter trial comparing 3 doses of Sumatriptan and Naproxen Sodium Tablets and placebo (Study 3). Patients enrolled in this trial were mostly female (59%) and white (81%), with a mean age of 15 years.

Patients were required to have at least a 6-month history of migraine attacks with or without aura usually lasting 3 hours or more when untreated. Following a single-blind, placebo run-in phase, placebo nonresponders were randomized to receive a single dose of either Sumatriptan and Naproxen Sodium Tablets 10/60 mg, 30/180 mg, 85/500 mg, or placebo. Patients were instructed to treat a single migraine attack with headache pain of moderate to severe intensity. No rescue medication was allowed within 2 hours postdose. Patients evaluated their headache pain 2 hours after taking 1 dose of study medication. Two-hour pain free was defined as a reduction in headache severity from moderate or severe pain to no pain at 2 hours postdose.

Results are summarized in Table 5. The percentage of patients who were pain free at 2 hours postdose was significantly greater among patients who received any of the 3 doses of Sumatriptan and Naproxen Sodium Tablets compared with placebo.

The percentage of pediatric patients who remained pain free without use of other medications 2 through 24 hours postdose was significantly greater after administration of a single dose of Sumatriptan and Naproxen Sodium Tablets 85/500 mg compared with placebo. A greater percentage of pediatric patients who received a single dose of 10/60 mg or 30/180 mg remained pain free 2 through 24 hours postdose compared with placebo.

Compared with placebo, the incidence of photophobia and phonophobia was significantly decreased 2 hours after the administration of a single dose of 85/500 mg, whereas, the incidence of nausea was comparable. There was a decreased incidence of photophobia, phonophobia, and nausea 2 hours after single-dose administration of 10/60 mg or 30/180 mg compared with placebo.

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Do not repackage; dispense and store in original container with desiccant.

Cardiovascular Thrombotic Events, Prinzmetal's Angina, Other Vasospasm-Related Events, Arrhythmias and Cerebrovascular Events

Advise patients to be alert for the symptoms of cardiovascular thrombotic effects such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for signs and symptoms of chest pain, shortness of breath, weakness, irregular heartbeat, significant rise in blood pressure, weakness and slurring of speech, and should be advised to report any of these symptoms to their health care provider immediately. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.3, 5.5, 5.6, 5.8)].

Gastrointestinal Bleeding, Ulceration, and Perforation

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding [see Warnings and Precautions (5.2)].

Hepatotoxicity

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, instruct patients to stop Sumatriptan and Naproxen Sodium Tablets and seek immediate medical therapy [see Warnings and Precautions (5.7)].

Anaphylactic Reactions

Inform patients that anaphylactic reactions have occurred in patients receiving the components of Sumatriptan and Naproxen Sodium Tablets. 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. Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help [see Contraindications (4), Warnings and Precautions (5.13)].

Serious Skin Reactions, including DRESS

Inform patients that Sumatriptan and Naproxen Sodium Tablets, like other NSAID-containing products, may increase the risk of serious skin side effects such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching and should ask for medical advice when observing any indicative signs or symptoms. Advise patients to stop taking Sumatriptan and Naproxen Sodium Tablets immediately if they develop any type of rash or fever and contact their healthcare providers as soon as possible [see Warnings and Precautions (5.14, 5.15)].

Fetal Toxicity

Inform pregnant women to avoid use of Sumatriptan and Naproxen Sodium Tablets and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with Sumatriptan and Naproxen Sodium Tablets is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours [see Warnings and Precautions (5.16), Use in Specific Populations (8.1)].

Lactation

Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].

Female Fertility

Advise females of reproductive potential who desire pregnancy that NSAIDs, including Sumatriptan and Naproxen Sodium Tablets, may be associated with a reversible delay in ovulation [see Use in Specific Populations (8.3)].

Heart Failure and Edema

Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see Warnings and Precautions (5.9)].

Concomitant Use with Other Triptans or Ergot Medications

Inform patients that use of Sumatriptan and Naproxen Sodium Tablets within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome with the use of Sumatriptan and Naproxen Sodium Tablets or other triptans, particularly during concomitant use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.11), Drug Interactions (7.1)].

Medication Overuse Headache

Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.10)].

Ability to Perform Complex Tasks

Treatment with Sumatriptan and Naproxen Sodium Tablets may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of Sumatriptan and Naproxen Sodium Tablets [see Adverse Reactions (6.1)].

Asthma

Advise patients with preexisting asthma to seek immediate medical attention if their asthma worsens after taking Sumatriptan and Naproxen Sodium Tablets. Patients with a history of aspirin-sensitive asthma should not take Sumatriptan and Naproxen Sodium Tablets [see Contraindications (4), Warnings and Precautions (5.18)].

Avoid Concomitant Use of NSAIDs

Inform patients that the concomitant use of Sumatriptan and Naproxen Sodium Tablets with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy [see Warnings and Precautions (5.2) and Drug Interactions (7)]. Alert patients that NSAIDs may be present in "over the counter" medications for treatment of colds, fever, or insomnia.

Use of NSAIDS and Low-Dose Aspirin

Inform patients not to use low-dose aspirin concomitantly with Sumatriptan and Naproxen Sodium Tablets until they talk to their healthcare provider [see Drug Interactions (7)].