Treximet

• Pernix Therapeutics, LLC

Treximet is part of the drug class:

• Selective serotonin

You should not use this medicine if you are allergic to sumatriptan (Imitrex) or naproxen (Aleve, Anaprox, Naprosyn), or if you have:

• uncontrolled high blood pressure;

• blood circulation problems (including poor blood flow to your arms and legs, stomach, intestines, or kidneys);

• a history of heart disease, angina (chest pain), recent or upcoming heart bypass surgery (CABG), heart attack, or stroke (including TIA or "mini-stroke");

• Wolff-Parkinson-White Syndrome (sudden fast heartbeats) or other heart rhythm disorder;

• severe liver disease;

• a history of asthma or severe allergic reaction after taking aspirin or an NSAID; or

• if you are in late pregnancy.

Naproxen can increase your risk of fatal heart attack or stroke, especially if you use it long term or take high doses, or if you have heart disease. Naproxen may also cause stomach or intestinal bleeding, which can be fatal. These conditions can occur without warning while you are using this medicine, especially in older adults.

Do not use sumatriptan and naproxen if you have used an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

Do not take sumatriptan and naproxen within 24 hours before or after using another migraine headache medicine, including:

• sumatriptan tablets or nasal spray, almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, or zolmitriptan; or

• ergot medicine such as ergotamine, dihydroergotamine, or methylergonovine.

To make sure sumatriptan and naproxen is safe for you, tell your doctor if you have:

• heart problems, high blood pressure, high cholesterol, fluid retention, diabetes, or if you smoke;

• a history of stomach ulcers or bleeding;

• epilepsy or other seizure disorder; or

• liver or kidney disease.

Taking this medicine during the last 3 months of pregnancy may harm the unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Sumatriptan and naproxen can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are taking this medication.

Sumatriptan and naproxen is not approved for use by anyone younger than 12 years old.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of sumatriptan and naproxen combination in children younger than 12 years of age. Safety and efficacy have not been established.

Geriatric

Use of sumatriptan and naproxen combination is not recommended in elderly patients with kidney problems, heart and blood vessel disease, or high blood pressure.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Almotriptan
• Bromocriptine
• Dihydroergotamine
• Eletriptan
• Ergoloid Mesylates
• Ergonovine
• Ergotamine
• Frovatriptan
• Furazolidone
• Iproniazid
• Isocarboxazid
• Ketorolac
• Linezolid
• Methylene Blue
• Methylergonovine
• Methysergide
• Moclobemide
• Naratriptan
• Phenelzine
• Procarbazine
• Rasagiline
• Rizatriptan
• Selegiline
• Tranylcypromine
• Zolmitriptan

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Alfentanil
• Amiloride
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Balsalazide
• Bemiparin
• Bendroflumethiazide
• Benzphetamine
• Benzthiazide
• Betamethasone
• Betrixaban
• Bismuth Subsalicylate
• Bivalirudin
• Bromfenac
• Budesonide
• Bufexamac
• Bumetanide
• Buprenorphine
• Butorphanol
• Cangrelor
• Celecoxib
• Ceritinib
• Certoparin
• Chlorothiazide
• Chlorthalidone
• Choline Magnesium Trisalicylate
• Choline Salicylate
• Cilostazol
• Citalopram
• Clomipramine
• Clonixin
• Clopamide
• Clopidogrel
• Codeine
• Cortisone
• Cyclopenthiazide
• Cyclosporine
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Dasabuvir
• Deflazacort
• Desipramine
• Desirudin
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexfenfluramine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Diazoxide
• Dibenzepin
• Diclofenac
• Diflunisal
• Digoxin
• Dihydrocodeine
• Dipyridamole
• Dipyrone
• Dolasetron
• Dothiepin
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Enoxaparin
• Eplerenone
• Epoprostenol
• Eptifibatide
• Escitalopram
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Feverfew
• Floctafenine
• Flufenamic Acid
• Fluocortolone
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Furosemide
• Ginkgo
• Gossypol
• Granisetron
• Heparin
• Hydrochlorothiazide
• Hydrocodone
• Hydrocortisone
• Hydroflumethiazide
• Hydromorphone
• Ibuprofen
• Iloprost
• Imipramine
• Indapamide
• Indomethacin
• Ketoprofen
• Lepirudin
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Magnesium Salicylate
• Meadowsweet
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Meperidine
• Mesalamine
• Methamphetamine
• Methotrexate
• Methyclothiazide
• Methylprednisolone
• Metolazone
• Milnacipran
• Mirtazapine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nadroparin
• Nalbuphine
• Naproxen
• Nefazodone
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Olsalazine
• Opipramol
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Palonosetron
• Paramethasone
• Parecoxib
• Parnaparin
• Paroxetine
• Pemetrexed
• Pentazocine
• Pentosan Polysulfate Sodium
• Pentoxifylline
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Phenyl Salicylate
• Piketoprofen
• Piroxicam
• Pixantrone
• Polythiazide
• Pralatrexate
• Prasugrel
• Prednisolone
• Prednisone
• Probenecid
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Reboxetine
• Remifentanil
• Reviparin
• Rivaroxaban
• Rofecoxib
• Salicylamide
• Salicylic Acid
• Salsalate
• Sertraline
• Sibutramine
• Sodium Salicylate
• Spironolactone
• St John's Wort
• Sufentanil
• Sulfasalazine
• Sulindac
• Tacrolimus
• Tapentadol
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Torsemide
• Tramadol
• Trazodone
• Treprostinil
• Triamterene
• Trichlormethiazide
• Trimipramine
• Trolamine Salicylate
• Valdecoxib
• Venlafaxine
• Vilazodone
• Vorapaxar
• Vortioxetine
• Warfarin
• Xipamide
• Ziprasidone

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Alacepril
• Atenolol
• Azilsartan
• Azilsartan Medoxomil
• Benazepril
• Betaxolol
• Bisoprolol
• Candesartan
• Captopril
• Carteolol
• Carvedilol
• Celiprolol
• Cilazapril
• Delapril
• Enalapril
• Enalaprilat
• Eprosartan
• Esmolol
• Fosinopril
• Imidapril
• Irbesartan
• Labetalol
• Levobunolol
• Lisinopril
• Losartan
• Metipranolol
• Metoprolol
• Moexipril
• Nadolol
• Nebivolol
• Olmesartan
• Oxprenolol
• Penbutolol
• Pentopril
• Perindopril
• Pindolol
• Practolol
• Propranolol
• Quinapril
• Ramipril
• Sotalol
• Spirapril
• Telmisartan
• Temocapril
• Timolol
• Trandolapril
• Valsartan
• Zofenopril

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Bleeding problems or
• Congestive heart failure or
• Edema (fluid retention) or
• Hypertension (high blood pressure), controlled or
• Inflammatory bowel disease (eg, Crohn disease, ulcerative colitis), history of or
• Kidney disease or
• Seizures, or history of or
• Stomach or bowel ulcers or bleeding, history of—Use with caution. May make these conditions worse.

• Angina (chest pain) or
• Aspirin-sensitive asthma or
• Aspirin sensitivity, history of or
• Basilar migraine (migraine with vision and hearing problems) or
• Heart attack, history of or
• Heart or blood vessel problems or
• Heart rhythm problems (eg, arrhythmia, Wolff-Parkinson-White syndrome) or
• Heart surgery (eg, coronary artery bypass graft [CABG] surgery) or
• Hemiplegic migraine (migraine with some paralysis) or
• Hypertension (high blood pressure), uncontrolled or
• Ischemic bowel disease (bowels have low blood supply) or
• Liver disease, severe or
• Peripheral vascular disease or
• Stroke, or history of or
• Transient ischemic attack, or history of—Should not be used in patients with these conditions.

• Coronary artery disease, history of or
• Diabetes or
• Hypercholesterolemia (high cholesterol in the blood) or
• Raynaud syndrome—Use with caution. The chance of side effects may be increased.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food. Take with food if it causes an upset stomach.
• Swallow whole. Do not chew, break, or crush.
• Take with liquids as early as you can after the attack has started.
• If your headache comes back after the first dose, 1 more dose may be taken 2 hours after the first one.
• Taking more of Treximet (a higher dose, more often) than your doctor told you to take may cause your headaches to become worse.
• Use care if you have risks for heart disease (high blood pressure, high cholesterol, overweight, high blood sugar or diabetes, cigarette smoking, man older than 40 years of age, other family members with early heart disease, woman after change of life). Talk with your doctor.
• This medicine is not meant to prevent or lower the number of migraine headaches you get. Talk with your doctor.
• Talk with your doctor before you drink alcohol.
• If you smoke, talk with your doctor.
• If you have asthma, talk with your doctor. You may be more sensitive to this medicine.
• If you are taking aspirin to help prevent a heart attack, talk with your doctor.
• High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Treximet with your other drugs.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.

What do I do if I miss a dose?

• This medicine is taken on an as needed basis. Do not take more than 2 tablets in 24 hours.

The following serious adverse reactions are described below and elsewhere in labeling:

• Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1)]
• GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2)]
• Arrhythmias [see Warnings and Precautions (5.3)]
• Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure [see Warnings and Precautions (5.4)]
• Cerebrovascular Events [see Warnings and Precautions (5.5)]
• Other Vasospasm Reactions [see Warnings and Precautions (5.6)]
• Hepatotoxicity [see Warnings and Precautions (5.7)]
• Hypertension [see Warnings and Precautions (5.8)]
• Heart Failure and Edema [see Warnings and Precautions (5.9)]
• Medication Overuse Headache [see Warnings and Precautions (5.10)]
• Serotonin Syndrome [see Warnings and Precautions (5.11)]
• Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.12)]
• Anaphylactic Reactions [see Warnings and Precautions (5.13)]
• Serious Skin Reactions [see Warnings and Precautions (5.14)]
• Hematological Toxicity [see Warnings and Precautions (5.16)]
• Exacerbation Asthma Related to Aspirin Sensitivity [see Warnings and Precautions (5.17)]
• Seizures [see Warnings and Precautions (5.18)]

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.

Adults

The adverse reactions reported below are specific to the clinical trials with Treximet 85/500 mg. See also the full prescribing information for naproxen and sumatriptan products.

Table 1 lists adverse reactions that occurred in 2 placebo-controlled clinical trials (Study 1 and 2) in adult patients who received 1 dose of study drug. Only adverse reactions that occurred at a frequency of 2% or more in any group treated with Treximet 85/500 mg and that occurred at a frequency greater than the placebo group are included in Table 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.

Pediatric Patients 12 to 17 Years of Age

In a placebo-controlled clinical trial that evaluated pediatric patients 12 to 17 years of age who received 1 dose of Treximet 10/60 mg, 30/180 mg, or 85/500 mg, adverse reactions occurred in 13% of patients who received 10/60 mg, 9% of patients who received 30/180 mg, 13% who received 85/500 mg, and 8% who received placebo. No patients who received Treximet experienced adverse reactions leading to withdrawal from the trial. The incidence of adverse reactions in pediatric patients 12 to 17 years of age was comparable across all 3 doses compared with placebo. Table 2 lists adverse reactions that occurred in a placebo-controlled trial in pediatric patients 12 to 17 years of age at a frequency of 2% or more with Treximet and were more frequent than the placebo group.

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), and it has the following structure:

The empirical formula is C14H21N3O2S∙C4H6O4, 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 C14H13NaO3, 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.

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.

NDC 65224-860-09
Rx only

Treximet®
sumatriptan/naproxen sodium Tablets

10 mg/60 mg

Do not repackage; dispense and store in
original container.

9 Tablets
Visit Treximet.com

Take Treximet exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger amounts or for longer than recommended. Use the lowest dose that is effective in treating your condition. Overuse of migraine headache medicine can actually make your headaches worse.

Take one (1) Treximet tablet as soon as you notice headache symptoms, or after an attack has already begun. You may take the medicine with or without food.

Do not crush, chew, or break the tablet. Swallow the pill whole.

If your headache does not go away, call your doctor before taking a second tablet. If your headache does not completely go away, or goes away and comes back, take a second Treximet tablet two (2) hours after the first.

If you are 12 to 17 years old: Do not take a second tablet without first asking your doctor.

You must wait at least 2 hours before you take a second tablet. Do not take more than 2 Treximet tablets in 24 hours. If your symptoms have not improved, call your doctor before taking any more tablets.

Call your doctor if you have more than five headaches in one month (30 days).

Store Treximet at room temperature away from moisture and heat.

Get emergency medical help if you have signs of an allergic reaction to Treximet: sneezing, runny or stuffy nose; wheezing or trouble breathing; hives; swelling of your face, lips, tongue, or throat.

Get emergency medical help if you have signs of a heart attack or stroke: chest pain spreading to your jaw or shoulder, sudden numbness or weakness on one side of the body, slurred speech, feeling short of breath.

Stop using Treximet and call your doctor at once if you have:

• numbness, tingling, pale or blue-colored appearance in your fingers or toes;

• leg cramps, burning or heavy feeling in your feet or legs;

• a seizure (convulsions);

• swelling, rapid weight gain, shortness of breath;

• stomach problems - sudden severe stomach pain (especially after eating), vomiting, bloody diarrhea, weight loss;

• signs of stomach bleeding - bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• liver problems - nausea, upper stomach pain, itching, tired feeling, flu-like symptoms, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• kidney problems - little or no urinating, painful or difficult urination, swelling in your feet or ankles;

• low red blood cells (anemia) - pale skin, feeling light-headed or short of breath; or

• severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common Treximet side effects may include:

• dizziness, drowsiness, weakness;

• irregular heartbeats;

• numbness or tingling;

• dry mouth, heartburn, nausea; or

• tight muscles, pain or pressure in your chest or throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ask your doctor before using Treximet if you take an antidepressant such as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, or vilazodone. Taking any of these medicines with naproxen may cause you to bruise or bleed easily.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• lithium;

• methotrexate;

• heparin or warfarin (Coumadin, Jantoven);

• heart or blood pressure medication, including a diuretic or "water pill"; or

• steroid medicine (such as prednisone).

This list is not complete. Other drugs may interact with sumatriptan and naproxen, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.