TREXIMET- sumatriptan succinate and naproxen sodium tablet, film coated
Pernix Therapeutics
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
Cardiovascular Thrombotic Events
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions (5.1)].
TREXIMET is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) Warnings and Precautions (5.1)] .
Gastrointestinal Bleeding, Ulceration, and Perforation
NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings and Precautions (5.2)].
1 INDICATIONS AND USAGE
TREXIMET is indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older.
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 TREXIMET, reconsider the diagnosis of migraine before TREXIMET is administered to treat any subsequent attacks.
TREXIMET is not indicated for the prevention of migraine attacks.
Safety and effectiveness of TREXIMET have not been established for cluster headache.
2 DOSAGE AND ADMINISTRATION
2.1 Dosage in Adults
The recommended dosage for adults is 1 tablet of TREXIMET 85/500 mg. TREXIMET 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 TREXIMET 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 TREXIMET 10/60 mg.
The maximum recommended dosage in a 24-hour period is 1 tablet of TREXIMET 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)].
DOSAGE FORMS AND STRENGTHS
10 mg sumatriptan/60 mg naproxen sodium, light-blue film-coated tablets, debossed on one side with "TREXIMET" and the other side with "10-60″.
85 mg sumatriptan/500 mg naproxen sodium, blue film-coated tablets, debossed on one side with "TREXIMET".
DESCRIPTION
TREXIMET contains sumatriptan (as the succinate), a selective 5-hydroxytryptamine1 (5-HT1 ) receptor subtype agonist, and naproxen sodium, a member of the arylacetic acid group of NSAIDs.
Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1),
The empirical formula is C14 H21 N3 O2 S∙C4 H6 O4 , representing a molecular weight of 413.5. Sumatriptan succinate is a white to off-white powder that is readily soluble in water and in saline.
Naproxen sodium is chemically designated as (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid, sodium salt,
The empirical formula is C14 H13 NaO3 , representing a molecular weight of 252.23. Naproxen sodium is a white-to-creamy white crystalline solid, freely soluble in water at neutral pH.
Each TREXIMET 85/500 mg tablet for oral administration contains 119 mg of sumatriptan succinate equivalent to 85 mg of sumatriptan and 500 mg of naproxen sodium. Each tablet also contains the inactive ingredients croscarmellose sodium, dibasic calcium phosphate, FD&C Blue No. 2, hypromellose, magnesium stearate, microcrystalline cellulose, povidone, sodium bicarbonate, talc, titanium dioxide, and triacetin.
Each TREXIMET 10/60 mg tablet for oral administration contains 14 mg of sumatriptan succinate equivalent to 10 mg of sumatriptan and 60 mg of naproxen sodium. Each tablet also contains the inactive ingredients croscarmellose sodium, dibasic calcium phosphate, FD&C Blue No. 2, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, povidone, sodium bicarbonate, talc, and titanium dioxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
TREXIMET 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.
TREXIMET has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of TREXIMET, 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
Blood Pressure
In a randomized, double-blind, parallel group, active control trial, TREXIMET 85/500 mg administered intermittently over 6 months did not increase blood pressure in a normotensive adult population (n = 122). However, significant elevation in blood pressure has been reported with 5-HT1 agonists and NSAIDs in patients with and without a history of hypertension.
HOW SUPPLIED/STORAGE AND HANDLING
TREXIMET 85/500 mg contains 119 mg of sumatriptan succinate equivalent to 85 mg of sumatriptan and 500 mg of naproxen sodium and is supplied as blue film-coated tablets debossed on one side with TREXIMET in bottles of 9 tablets with desiccant (NDC 65224-850-09).
TREXIMET 10/60 mg contains 14 mg of sumatriptan succinate equivalent to 10 mg of sumatriptan and 60 mg of naproxen sodium and is supplied as light-blue film-coated tablets debossed on one side with TREXIMET and the other side with 10-60 in bottles of 9 tablets with desiccant (NDC 65224-860-09).
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.
