Treximet Information
Treximet () Description
Treximet () contains sumatriptan (as the succinate), a selective 5-hydroxytryptamine (5-HT) receptor subtype agonist, and naproxen sodium, a member of the arylacetic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs).
Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:
The empirical formula is CHNOS•CHO, 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, and it has the following structure:
The empirical formula is CHNaO, 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 () 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, dextrose monohydrate, dibasic calcium phosphate, FD&C Blue No. 2, lecithin, magnesium stearate, maltodextrin, microcrystalline cellulose, povidone, sodium bicarbonate, sodium carboxymethylcellulose, talc, and titanium dioxide.
Treximet () Clinical Pharmacology
Treximet () contains sumatriptan, a 5-HT receptor agonist that mediates vasoconstriction of the human basilar artery and vasculature of human dura mater, which correlates with the relief of migraine headache. It also contains naproxen, an NSAID that inhibits the synthesis of inflammatory mediators. Therefore, sumatriptan and naproxen contribute to the relief of migraine through pharmacologically different mechanisms of action.
Sumatriptan is a 5-HT receptor agonist that binds with high affinity to 5-HT and 5-HT receptors. Sumatriptan has only a weak affinity for 5-HT, 5-HT, and 5-HT receptors and no significant affinity (as measured using standard radioligand binding assays) or pharmacological activity at 5-HT, 5-HTor 5-HT receptor subtypes or at alpha-, alpha-, or beta-adrenergic; dopamine; dopamine; muscarinic; or benzodiazepine receptors. In addition to causing vasoconstriction, experimental data from animal studies show that sumatriptan also activates 5-HT receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels. Such an action may contribute to the antimigrainous effect of sumatriptan in humans. In the anesthetized dog, sumatriptan selectively reduces carotid arterial blood flow with little or no effect on arterial blood pressure or total peripheral resistance.
Naproxen sodium is an NSAID with analgesic and antipyretic properties. The sodium salt of naproxen has been developed as a more rapidly absorbed formulation of naproxen for use as an analgesic. The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.
Treximet () is a formulation of 85 mg of sumatriptan (as sumatriptan succinate) and 500 mg of naproxen sodium with a distinct pharmacokinetic profile. C (median, range) for sumatriptan following administration of Treximet () occurs at approximately 1 hour (0.3 to 4.0 hours). C (median, range) for naproxen following administration of Treximet () occurs at approximately 5 hours (0.3 to 12 hours). The sumatriptan half-life is approximately 2 hours (15% to 43% CV) and the naproxen half-life is approximately 19 hours (13% to 15% CV). The mean C for sumatriptan when given as Treximet () is similar to that of sumatriptan when given as IMITREX (sumatriptan succinate) Tablets 100 mg alone. The median sumatriptan T is only slightly different (1 hour for Treximet () and 1.5 hours for IMITREX). The C for naproxen is approximately 36% lower, and the T occurs approximately 4 hours later from Treximet () than from ANAPROX DS (naproxen sodium tablets) 550 mg. AUC values for sumatriptan and for naproxen are similar for Treximet () compared to IMITREX or ANAPROX DS, respectively. In a crossover study in 16 patients, the pharmacokinetics of both components administered as Treximet () were similar during a migraine attack and during a migraine-free period.
Naproxen is rapidly and completely absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%.
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The volume of distribution of naproxen is 0.16 L/kg. At therapeutic levels naproxen is greater than 99% albumin bound. At doses of naproxen greater than 500 mg/day, there is a less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough C = 36.5, 49.2, and 56.4 mg/L with 500, 1,000, and 1,500 mg daily doses of naproxen, respectively). However, the concentration of unbound naproxen continues to increase proportionally to dose.
Naproxen is extensively metabolized to 6-0-desmethyl naproxen, and both parent and metabolites do not induce metabolizing enzymes.
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The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen (less than 1%), 6-0-desmethyl naproxen (less than 1%), or their conjugates (66% to 92%). The plasma half-life of the naproxen anion in humans is approximately 19 hours. The corresponding half-lives of both metabolites and conjugates of naproxen are shorter than 12 hours, and their rates of excretion have been found to coincide closely with the rate of naproxen disappearance from the plasma. In patients with renal failure, metabolites may accumulate (see PRECAUTIONS: Renal Effects).
Minimal change in clinical effect would be expected with regard to sumatriptan as it is largely metabolized to an inactive substance.
Since naproxen and its metabolites and conjugates are primarily excreted by the kidney, the potential exists for naproxen metabolites to accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment.
The pharmacokinetics of oral sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in patients with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years).
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No formal drug interaction studies have been conducted with Treximet () .
Treximet () Clinical Trials
The efficacy of Treximet () in providing relief from migraine was demonstrated in 2 randomized, double-blind, multicenter, parallel-group trials utilizing placebo and each individual active component of Treximet () (sumatriptan and naproxen sodium) as comparison treatments. Patients enrolled in these 2 trials were predominately female (87%) and Caucasian (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 the 2 controlled clinical trials are summarized in Table 1. In both trials, the percentage of patients achieving headache pain relief 2 hours after treatment was significantly greater among patients receiving Treximet () (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 Treximet () (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 Treximet () is shown in Figure 1.
Compared with placebo, there was a decreased incidence of photophobia, phonophobia, and nausea 2 hours after the administration of Treximet () . The estimated probability of taking a rescue medication over the first 24 hours is shown in Figure 2.
Treximet () was more effective than placebo regardless of the presence of aura; duration of headache prior to treatment; gender, age, or weight of the patient; or concomitant use of oral contraceptives or common migraine prophylactic drugs (e.g., beta-blockers, anti-epileptic drugs, tricyclic antidepressants).
Treximet () Indications And Usage
Treximet () is indicated for the acute treatment of migraine attacks with or without aura in adults. Carefully consider the potential benefits and risks of Treximet () and other treatment options when deciding to use Treximet () .
Treximet () is 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 Treximet () have not been established for cluster headache.
Treximet () Contraindications
Treximet () 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 Treximet () , nor should patients who have had coronary artery bypass graft (CABG) surgery. 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: Cardiovascular Effects).
Treximet () should not be given to patients with uncontrolled hypertension because the components have been shown to increase blood pressure.
Concurrent administration of MAO-A inhibitors or use of Treximet () within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated (see CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions).
Treximet () and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other (see PRECAUTIONS: Drug Interactions).
Since Treximet () contains sumatriptan, it should not be administered within 24 hours of another 5-HT agonist.
Treximet () should not be administered to patients with hemiplegic or basilar migraine.
Treximet () is contraindicated in patients with hepatic impairment (see CLINICAL PHARMACOLOGY: Special Populations, PRECAUTIONS: Hepatic Effects, and PRECAUTIONS: Geriatric Use).
Treximet () is contraindicated in patients who have had allergic reactions to prescription as well as to over-the-counter products containing naproxen. It is also contraindicated in patients in whom aspirin or other nonsteroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis, and nasal polyps. Anaphylactic/anaphylactoid reactions to naproxen, whether of the true allergic type or the pharmacologic idiosyncratic type (e.g., aspirin hypersensitivity syndrome), usually but not always occur in patients with a known history of such reactions. Both types of reactions have the potential of being fatal. Therefore, careful questioning of patients for medical conditions such as asthma, nasal polyps, urticaria, and hypotension associated with NSAIDs before starting therapy is important. In addition, if such symptoms occur during therapy, treatment should be discontinued (see WARNINGS: Anaphylactic/Anaphylactoid Reactions and PRECAUTIONS: Preexisting Asthma).
Treximet () is contraindicated in patients with hypersensitivity to sumatriptan, naproxen, or any other component of the product.
Treximet () Warnings
Treximet () should only be used where a clear diagnosis of migraine headache has been established.
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 Treximet () 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) immediately following first-time use of Treximet () in patients with risk factors.
It is recommended that patients who are intermittent long-term users of Treximet () and who have or acquire risk factors predictive of CAD as described above undergo periodic cardiovascular evaluation as they continue to use Treximet () .
The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to sumatriptan-containing products.
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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 cases, however, where there has been known underlying coronary artery disease, the relationship is uncertain.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious gastrointestinal events (see WARNINGS: Risk of Gastrointestinal Ulceration, Bleeding, and Perforation With Nonsteroidal Anti-inflammatory Drug Therapy).
Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without a history of hypertension receiving sumatriptan. Sumatriptan-containing products should be administered with caution to patients with controlled hypertension as transient increases in blood pressure and peripheral vascular resistance have been observed.
NSAID-containing products can 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 thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. The potential effect on blood pressure associated with long-term use of Treximet () has not been studied. Blood pressure should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Treximet () contains an NSAID. NSAID-containing products can 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. These trends continue with longer duration of use, increasing the likelihood of developing a serious gastrointestinal event at some time during the course of therapy. However, even short-term therapy is not without risk. Among 3,302 patients with migraine who received Treximet () in premarketing 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.
NSAID-containing products, including Treximet () , should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing gastrointestinal bleeding compared to patients with neither of these risk factors. Other factors that increase the risk for gastrointestinal bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal gastrointestinal events are in elderly or debilitated patients, and therefore special care should be taken in treating this population.
To minimize the potential risk for an adverse gastrointestinal event in patients treated with an NSAID-containing product, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of gastrointestinal ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious gastrointestinal adverse event is suspected. This should include discontinuation of the NSAID until a serious gastrointestinal adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.
NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
As with other NSAID-containing products, anaphylactic/anaphylactoid reactions may occur in patients without known prior exposure to naproxen. Treximet () 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, PRECAUTIONS: Preexisting Asthma, and PRECAUTIONS: Drug Interactions).
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 (see CONTRAINDICATIONS). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.
Treximet () Precautions
Treximet () and other naproxen-containing products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.
Treximet () is contraindicated in patients with hepatic impairment (see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY).
The ability of Treximet () to interfere with commonly employed clinical laboratory tests has not been investigated.
Sumatriptan is not known to interfere with commonly employed clinical laboratory tests. Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined.
The administration of naproxen sodium may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used.
Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).
The carcinogenic potential of sumatriptan was evaluated in oral carcinogenicity studies in mice (78 weeks) and rats (104 weeks). The highest dose administered to mice and rats (160 mg/kg/day) is approximately 9 and 18 times, respectively, the recommended human oral daily dose of 85 mg sumatriptan on a mg/m basis. There was no evidence of an increase in tumors in either species related to sumatriptan administration.
The carcinogenic potential of naproxen sodium was evaluated in a 2-year oral carcinogenicity study in rats at doses of 8, 16, and 24 mg/kg/day and in another 2-year oral carcinogenicity study in rats at a dose of 8 mg/kg/day. No evidence of tumorigenicity was found in either study, at doses up to approximately 0.5 times the recommended human oral daily dose of 500 mg/day naproxen sodium on a mg/m basis.
The combination of sumatriptan and naproxen sodium was negative in an in vitro mouse lymphoma tk assay in the presence and absence of metabolic activation. However, in separate in vitro mouse lymphoma tk assays, naproxen sodium alone was reproducibly positive in the presence of metabolic activation.
Naproxen sodium alone and in combination with sumatriptan was positive in an in vitro clastogenicity assay in mammalian cells in the presence and absence of metabolic activation. The clastogenic effect for the combination was reproducible within this assay and was greater than observed with naproxen sodium alone. Sumatriptan alone was negative in these assays.
Chromosomal aberrations were not induced in peripheral blood lymphocytes following 7 days of twice-daily dosing with Treximet () in human volunteers.
In previous studies, sumatriptan alone was not mutagenic in 2 gene mutation assays (the Ames test and the in vitro Chinese Hamster V79/HGPRT assay) and was not clastogenic in 2 cytogenetics assays (the in vitro human lymphocyte assay and the in vivo rat micronucleus assay).
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 0.5 times the recommended human oral daily dose of 85 mg sumatriptan on a mg/m basis. It is not clear whether the problem is associated with treatment of the males or females or both combined. In a similar study of sumatriptan by the subcutaneous route there was no evidence of impaired fertility at doses up to 60 mg/kg/day.
Pregnancy Category C. In developmental toxicity studies in rabbits, oral treatment with sumatriptan combined with naproxen sodium (5/9, 25/45, or 50/90 mg/kg/day sumatriptan/naproxen sodium) or each drug alone (50/0 or 0/90 mg/kg/day sumatriptan/naproxen sodium) resulted in decreased fetal body weight in all treated groups and in increased embryofetal death at the highest dose of naproxen, alone and in combination with sumatriptan. Naproxen sodium, alone and in combination with sumatriptan, increased the total incidences of fetal abnormalities at all doses and increased the incidences of specific malformations (cardiac interventricular septal defect in the 50/90-mg/kg/day group, fused caudal vertebrae in the 50/0- and 0/90-mg/kg/day groups) and variations (absent intermediate lobe of the lung, irregular ossification of the skull, incompletely ossified sternal centra) in the 50/0- and 0/90-mg/kg/day groups. A no-effect dose for development toxicity in rabbits was not established. The lowest effect dose was 5/9 mg/kg/day sumatriptan/naproxen sodium, which was associated with plasma exposures (AUC) to sumatriptan and naproxen that were 1.4 and 0.14 times, respectively, those attained at the maximum recommended human oral daily dose of 85 mg sumatriptan and 500 mg naproxen sodium.
In previous developmental toxicity studies in rats and rabbits, oral treatment with sumatriptan was associated with embryolethality, fetal abnormalities, and pup mortality. Oral treatment of pregnant rats with sumatriptan during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities and decreased pup survival at doses of 250 mg/kg/day or higher. The highest no-effect dose was approximately 60 mg/kg/day, which is approximately 7 times the recommended human oral daily dose of 85 mg sumatriptan on a mg/mbasis. Oral treatment of pregnant rabbits with sumatriptan during the period of organogenesis resulted in an increased incidence of cervicothoracic vascular and skeletal abnormalities at a dose of 50 mg/kg/day and embryolethality at 100 mg/kg/day. The highest no-effect dose for embryotoxicity in rabbits was 15 mg/kg/day, or approximately 3 times the recommended human oral daily dose of 85 mg sumatriptan on a mg/m basis.
Inhibitors of prostaglandin synthesis (including naproxen) are known to delay parturition. Because of this and the known effects of drugs of this class on the human fetal cardiovascular system (closure of the ductus arteriosus), use during third trimester should be avoided.
There are no adequate and well-controlled studies in pregnant women.
Treximet () should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Treximet () Adverse Reactions
The adverse reactions reported below are specific to the clinical trials with Treximet () . See also the full prescribing information for naproxen and sumatriptan products.
Table 2 lists adverse events that occurred in 2 placebo-controlled clinical trials evaluating patients who took at least 1 dose of study drug. Only events that occurred at a frequency of 2% or more with Treximet () and were more frequent 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.
Other events that occurred in more than 1% of patients receiving Treximet () and occurred at a frequency greater than the placebo group included asthenia, feeling hot, muscle tightness, and palpitations.
Treximet () was generally well tolerated. Most adverse reactions were mild and transient. 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.
The occurrence of less commonly reported adverse clinical events is presented in this section. Because the reports include events observed in an open-label, long-term safety study in which Treximet () was used as needed for up to 12 months, the role of Treximet () 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 Treximet () and reported an event divided by the total number of patients (N = 3,302) exposed to Treximet () . Events listed in the previous table and text are not included below. Those events described too generally to be informative or those unlikely to be associated with the use of Treximet () are excluded. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are 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.
Treximet () Drug Abuse And Dependence
The potential for abuse with Treximet () has not been studied.
One clinical study with sumatriptan succinate injection enrolling 12 patients with a history of substance abuse failed to induce subjective behavior and/or physiologic response ordinarily associated with drugs that have an established potential for abuse.
Treximet () Overdosage
Because strategies for the management of overdose are continually evolving, it is advisable to contact a Poison Control Center to determine the latest recommendations for the management of an overdose of any drug.
There have been no reports of overdosage with Treximet () . Since sumatriptan and naproxen have pharmacologically different actions, it is difficult to predict how an individual will respond to an overdosage with Treximet () .
Patients (N = 670) have received single oral doses of 140 to 300 mg of sumatriptan without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 to 400 mg without serious adverse events. Overdose of sumatriptan 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.
Significant naproxen overdosage may be characterized by lethargy, dizziness, drowsiness, epigastric pain, abdominal discomfort, heartburn, indigestion, nausea, transient alterations in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation, or vomiting. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. Because naproxen sodium may be rapidly absorbed, high and early blood levels should be anticipated. A few patients have experienced seizures, but it is not clear whether or not these were drug related. It is not known what dose of the drug would be life threatening.
In animals 0.5 g/kg of activated charcoal was effective in reducing plasma levels of naproxen. Patients should be managed by symptomatic and supportive care. There are no specific antidotes. Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding. It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose. Forced diuresis, alkalinization of urine, or hemoperfusion may not be useful due to high protein binding.
Treximet () Dosage And Administration
Treximet () is a fixed combination containing doses of sumatriptan (85 mg) and naproxen sodium (500 mg) within the approved dosage ranges of the individual components (25 to 100 mg of sumatriptan and 220 to 825 mg of naproxen sodium). Treximet () contains a dose of sumatriptan higher than the lowest effective dose. Individuals may vary in response to doses of sumatriptan. The choice of the dose of sumatriptan, and of the use of a fixed combination such as in Treximet () should therefore 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 events. Carefully consider the potential benefits and risks of Treximet () and other treatment options when deciding to use Treximet () .
The recommended dose is 1 tablet. In controlled clinical trials, single doses of Treximet () were effective for the acute treatment of migraine in adults (see CLINICAL TRIALS).
The efficacy of taking a second dose has not been established. Do not take more than 2 Treximet () tablets in 24 hours. Dosing of tablets should be at least 2 hours apart. The safety of treating an average of more than 5 migraine headaches in a 30-day period has not been established.
Treximet () may be administered with or without food. Tablets should not be split, crushed, or chewed.
The combined use of Treximet () with MAO-A inhibitors or use of Treximet () within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated (see CONTRAINDICATIONS, CLINICAL PHARMACOLOGY: Drug Interactions, PRECAUTIONS: Drug Interactions).
Treximet () and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other. Treximet () and other 5-HT agonists should not be administered within 24 hours of each other (see CONTRAINDICATIONS and PRECAUTIONS: Drug Interactions).
Treximet () is contraindicated in patients with hepatic impairment (see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY: Special Populations).
Treximet () is not recommended for use in patients with creatinine clearance less than 30 mL/min (see CLINICAL PHARMACOLOGY: Special Populations and PRECAUTIONS: Renal Effects).
Treximet () How Supplied
Treximet () 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 in compact containers of 9 tablets with a specially formulated, non-removable desiccant (NDC 21695-954-09).
Treximet ()
Treximet () Principal Display Panel
