TRILISATE Tablets/ Liquid are nonsteroidal, anti-inflammatory preparations containing choline magnesium trisalicylate which is freely soluble in water. The absolute structure of choline magnesium trisalicylate is not known at this time. Choline magnesium trisalicylate has a molecular formula of C₂₆H₂₉O₁₀NMg, and a molecular weight of 539.8.

This substance when dissolved in water would appear to form 5 ions (1 choline ion, 1 magnesium ion and 3 salicylate ions).

TRILISATE Tablets/ Liquid are available in scored, pale pink 500 mg tablets; in scored, white, film-coated 750 mg tablets, and in scored, red, film-coated 1000 mg tablets. TRILISATE Liquid is a cherry cordial-flavored liquid providing 500 mg salicylate content per teaspoonful (5 ml) for oral administration.

Each 500 mg tablet contains 293 mg of choline salicylate combined with 362 mg of magnesium salicylate to provide 500 mg salicylate content.

Each 750 mg tablet contains 440 mg of choline salicylate combined with 544 mg of magnesium salicylate to provide 750 mg salicylate content.

Each 1000 mg tablet contains 587 mg of choline salicylate combined with 725 mg magnesium salicylate to provide 1000 mg salicylate content.

TRILISATE Liquid contains 293 mg of choline salicylate combined with 362 mg of magnesium salicylate to provide 500 mg salicylate per teaspoonful (5 ml) in a clear amber, cherry cordial-flavored vehicle.

Inactive Ingredients

Each 500 mg tablet contains: Carboxymethylcellulose sodium, Corn starch, Edetate disodium, FD& C Yellow No. 6, Stearic acid, and other ingredients.

Each 750 mg tablet contains: Carboxymethylcellulose sodium, Edetate disodium, Hydroxypropyl methylcellulose, Polyethylene glycol, Polysorbate 20, Stearic acid, Talc, Titanium dioxide, and other ingredients.

Each 1000 mg tablet contains: Carboxymethylcellulose sodium, Edetate disodium, FD& C Red No. 40, FD& C Yellow No. 6, FD& C Blue No. 2, Hydroxypropyl methylcellulose, Polyethylene glycol, Polysorbate 20, Polysorbate 80, Stearic acid, Talc, Titanium dioxide, and other ingredients.

Each teaspoonful (5 ml) of Liquid contains: Caramel, Carboxymethylcellulose sodium, Edetate disodium, FD& C Yellow No. 6, Glycerin, High fructose corn syrup, Potassium sorbate, Water, and Artificial flavors.

Osteoarthritis, Rheumatoid Arthritis and Acute Painful Shoulder

Salicylates are considered the base therapy of choice in the arthritides; and TRILISATE preparations are indicated for the relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and other arthritides. TRILISATE Tablets or Liquid are indicated in the long-term management of these diseases and especially in the acute flare of rheumatoid arthritis. TRILISATE Tablets or Liquid are also indicated for the treatment of acute painful shoulder.

TRILISATE preparations are effective and generally well tolerated, and are logical choices whenever salicylate treatment is indicated. They are particularly suitable when a once-a-day or b.i.d. dosage regimen is important to patient compliance; when gastrointestinal intolerance to aspirin is encountered; when gastrointestinal microbleeding or hematologic effects of aspirin are considered a patient hazard; and when interference (or the risk of interference) with normal platelet function by aspirin or by propionic acid derivatives is considered to be clinically undesirable. Use of TRILISATE Liquid is appropriate when a liquid dosage form is preferred, as in the elderly patient.

The efficacy of TRILISATE preparations has not been studied in those patients who are designated by the American Rheumatism Association as belonging in Functional Class IV (incapacitated, largely or wholly bedridden or confined to a wheelchair, with little or no self-care).

Analgesic and Antipyretic Action

TRILISATE Tablets/ Liquid are also indicated for the relief of mild to moderate pain and for antipyresis. In children, TRILISATE preparations are indicated for conditions requiring anti- inflammatory or analgesic action such as juvenile rheumatoid arthritis and other appropriate conditions.

ADULTS

In rheumatoid arthritis, osteoarthritis, the more severe arthritides, and acute painful shoulder, the recommended starting dosage is 1500 mg given b.i.d. Some patients may be treated with 3000 mg given once per day (h.s.) In the elderly patient, a daily dosage of 2250 mg given as 750 mg t.i.d. may be efficacious and well tolerated. Dosage should be adjusted in accordance with the patients response. In patients with renal dysfunction, monitor salicylate levels and adjust dose accordingly.

For mild to moderate pain or for antipyresis, the usual dosage is 2000 mg to 3000 mg daily in divided doses (b.i.d.). Based on patient response or salicylate blood levels, dosage may be adjusted to achieve optimum therapeutic effect. Salicylate blood levels should be in the range of 15 to 30 mg/ 100 mL for anti-inflammatory effect and 5 to 15 mg/ 100 mL for analgesia and antipyresis.

Each 500 mg tablet or teaspoonful is equivalent in salicylate content to 10 g of aspirin; each 750 mg tablet, to 15 g of aspirin; and each 1000 mg tablet, to 20 g of aspirin.

If the physician prefers, the recommended daily dosage may be administered on a t.i.d. schedule.

As with other therapeutic agents, individual dosage adjustment is advisable, and a number of patients may require higher or lower dosages than those recommended. Certain patients require 2 to 3 weeks of therapy for optimal effect.

CHILDREN

Usual daily dose for children for anti- inflammatory or analgesic action:

TRILISATE 500 mg Tablets/ Liquid and TRILISATE 750 mg and 1000 mg Tablets, 50 mg/ kg/ day.

Total daily doses should be administered in divided doses (b.i.d.). Doses of TRILISATE preparations are calculated as the total daily dose of 50 mg/ kg/ day for children of 37 kg body weight or less and 2250 mg/ day for heavier children.

TRILISATE Liquid is available for greater convenience in treating younger patients and those adult patients unable to wswallow a solid dosage form.

NDC 0034-0500-80: TRILISATE 500 mg Tablets (pale pink, scored) supplied in bottles of 100 tablets.

NDC 0034-0500-50: TRILISATE 500 mg Tablets (pale pink, scored) supplied in bottles of 500 tablets.

NDC 0034-0500-10: TRILISATE 500 mg Tablets (pale pink, scored) supplied in unit dose packaging with 10 tablets per card. Ten cards are packed in each carton; 10 cartons are packed in each shipper.

NDC 0034-0505-80: TRILISATE 750 mg Tablets (scored, white, film-coated) in bottles of 100 tablets.

NDC 0034-0505-50: TRILISATE 750 mg Tablets (scored, white, film-coated) in bottles of 500 tablets.

NDC 0034-0505-10: TRILISATE 750 mg Tablets (scored, white, film-coated) supplied in unit dose packaging with 10 tablets per card. Ten cards are packed in each carton; 10 cartons are packed in each shipper.

NDC 0034-0510-60: TRILISATE 1000 mg Tablets (scored, red, film-coated) in bottles of 60 tablets.

NDC 0034-0510-80: TRILISATE 1000 mg Tablets (scored, red, film-coated) in bottles of 100 tablets.

NDC 0034-0520-80: TRILISATE Liquid in bottles of 8 fl. oz. (237 mL).

Store at controlled room temperature 59° to 86° F( 15° to 30° C).

CAUTION: Federal law prohibits dispensing without a prescription.

REFERENCES

1. Szczeklik, A et al; Choline magnesium trisalicylate in patients with aspirin- induced asthma; Eur Respir J; 3: 535- 539, 1990.

2. Zucker, MB and Rothwell KB; Differential influences of salicylate compounds on platelet aggregation and serotonin release; Current Therapeutic Research; 23(2), Feb 1987.

3. Stuart, JJ and Pisko, EJ; Choline magnesium trisalicylate does not impair platelet aggregation; Pharmatherapeutica; 2(8): 547, 1981.

4. Danesh, BJZ, Saniabadi, AR, Russell, RI et al; Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies; Scottish Medical Journal; 32: 167- 168, 1987.

5. Danesh, BJZ, McLaren, M, Russell, RI et al; Does non- acetylated salicylate inhibit thromboxane biosynthesis in human platelets? Scottish Medical Journal; 33: 315- 316, 1988.

6. Danesh, BJZ, McLaren, M, Russell, RI etal; Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety; Haemostasis; 19: 169- 173, 1989.

7. Data on file. Medical Department. The Purdue Frederick Company, 1989.

8. Blechman, WJ, and Lechner, BL; Clinical comparative evalua- tion of choline magnesium trisalicylate and acetylsalicylic acid in rheumatoid arthritis; Rheumatology and Rehabilitation; 18: 119- 124, 1979.

9. McLaughlin, G; Choline magnesium trisalicylate vs. naproxen in rheumatoid arthritis; Current Therapeutic Research; 32(4): 579- 585, 1982.

10. Ehrlich, GE; Miller, SB; and Zeiders, RS; Choline magnesium trisalicylate vs. ibuprofen in rheumatoid arthritis; Rheumatol- ogy and Rehabilitation; 19: 30- 41, 1980.

11. Goldenberg, A; Rudnicki, AD, and Koonce, ML; Clinical com- parison of efficacy and safety of choline magnesium trisalicylate and indomethacin in treating osteoarthritis; Current Therapeutic Research; 24(3): 245- 260, 1978.

12. Guerin, BK and Burnstein, SL; Conservative therapy of acute painful shoulder; Orthopedic Review; XI (7) :29- 37, 1982.

The most frequent adverse reactions observed with TRILISATE preparations in clinical trials (7- 12) are tinnitus and gastrointestinal complaints (including nausea, vomiting, gastric upset, indigestion, heartburn, diarrhea, constipation and epigastric pain). These occur in less than twenty percent (20%) of patients. Should tinnitus develop, reduction of daily dosage is recommended until the tinnitus is resolved. Less frequent adverse reactions, occurring in less than two percent (2%) of patients, are: hearing impairment, headache, lightheadedness, dizziness, drowsiness, and lethargy. Adverse reactions occurring in less than one percent (1%) of patients are: gastric ulceration, positive fecal occult blood, elevation in serum BUN and creatinine, rash, pruritus, anorexia, weight gain, edema, epistaxis and dysgeusia.

Spontaneous reporting has yielded isolated or rare reports of the following adverse experiences: duodenal ulceration, elevated hepatic transaminases, hepatitis, esophagitis, asthma, erythema multiforme, urticaria, ecchymoses, irreversible hearing loss and/ or tinnitus, mental confusion, hallucinations.

DRUG ABUSE AND DEPENDENCE

Drug abuse and dependence have not been reported with TRILISATE preparations.

Foods and drugs that alter urine pH may affect renal clearance of salicylate and plasma salicylate concentrations. Raising urine pH, as with chronic antacid use, can enhance renal salicylate clearance and diminish plasma salicylate concentration; urine acidification can decrease urinary salicylate excretion and increase plasma levels.

When salicylate drug products are concurrently dosed with other plasma protein bound drug products, adverse effects may result. Although TRILISATE preparations are a rational choice for anti- inflammatory and analgesic therapy in patients on oral anticoagulants due to their demonstrated lack of effect in vivo and in vitro on platelet aggregation, bleeding time, platelet count, prothrombin time, and serum thromboxane B₂ generation (7), the potential exists for increased levels of unbound warfarin with their concurrent use. Prothrombin time should be closely monitored and warfarin dose appropriately adjusted when therapy with TRILISATE preparations is initiated. The effect of TRILISATE on blood prothrombin levels has not been established. Salicylates may increase the therapeutic as well as toxic effects of methotrexate, particularly when administered in chemotherapeutic doses, by inhibition of renal methotrexate excretion and by displacement of plasma protein bound methotrexate. Caution should be exercised in administering TRILISATE to rheumatoid arthritis patients on methotrexate. When sulfonylurea oral hypoglycemic agents are co- administered with salicylates, the hypoglycemic effect may be enhanced via increased insulin secretion or by displacement of sulfonylurea agents from binding sites. Insulin- treated diabetics on high doses of salicylates should also be closely monitored for a similar hypoglycemic response. Other drugs with which salicylate competes for protein binding sites, and whose plasma concentration or free fraction may be altered by concurrent salicylate administration, include the following: phenytoin, valproic acid, and carbonic anhydrase inhibitors.

The efficacy of uricosuric agents may be decreased when administered with salicylate products. Although low doses of salicylate (1 to 2 grams per day) have been reported to decrease urate excretion and elevate plasma urate concentrations, intermediate doses (2 to 3 grams per day) usually do not alter urate excretion. Larger salicylate doses (over 5 grams per day) can induce uricosuria and lower plasma urate levels.

Corticosteroids can reduce plasma salicylate levels by increasing renal elimination and perhaps by also stimulating hepatic metabolism of salicylates. By monitoring plasma salicylate levels, salicylate dosage may be titrated to accommodate changes in corticosteroid dose or to avoid salicylate toxicity during corticosteroid taper.

Reye Syndrome is a rare but serious disease which may develop in children and teenagers who have chicken pox, influenza, or flu symptoms. While the cause of Reye Syndrome is unknown, some studies suggest a possible association between the development of Reye Syndrome and the use of medicines containing acetylated salicylates or aspirin. TRILISATE Tablets and Liquid are a combination of choline salicylate and magnesium salicylate which are nonacetylated salicylates, and there have been no reported cases associating TRILISATE with Reye Syndrome. Nevertheless, TRILISATE, as a salicylate-containing product, is not recommended for use in children and teenagers with chicken pox, influenza or flu symptoms.

General

As with other salicylates and non- steroidal anti-inflammatory drugs, TRILISATE preparations should be used with caution in patients with acute or chronic renal insufficiency, with acute or chronic hepatic dysfunction, or with gastritis or peptic ulcer disease.

Although reports exist of cross reactivity, including bronchospasm, with the use of non-acetylated salicylate products in aspirin- sensitive patients, TRILISATE preparations were found to be well tolerated with regard to pulmonary function and respiratory symptoms when these parameters were monitored in a group of documented aspirin-sensitive asthmatics dosed with TRILISATE in both controlled and open label studies.¹

Concurrent use of other salicylate-containing products and TRILISATE preparations can lead to an increase in plasma salicylate concentration and may result in potentially toxic salicylate levels.

Laboratory Tests

Plasma salicylate levels can be periodically assessed during treatment with TRILISATE preparations to determine whether a therapeutically effective anti-inflammatory concentration of 15 to 30 mg/ 100 ml (150-300 µg/ mL) is being maintained. Manifestations of systemic salicylate intoxication are usually not seen until the concentration exceeds 30 mg/100 mL. However, such tests rarely differentiate between the active free and inactive protein bound salicylate components. Since protein binding of salicylate is affected by age, nutritional status, competitive binding of other drugs, and underlying disease (e.g. rheumatoid arthritis), plasma salicylate level determinations may not always accurately reflect efficacious or toxic levels of active free salicylate. Acidification of the urine can significantly diminish the renal clearance of salicylate and increase plasma salicylate concentrations.

Drug/ Laboratory Test Interactions

Free T₄ values may be increased in patients on salicylate drug products due to competitive plasma protein binding; a concurrent decrease in total plasma T₄ may be observed. Thyroid function is not affected.

Carcinogenesis

No long-term animal studies have been performed with TRILISATE to evaluate its carcinogenic potential.

Use in Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with TRILISATE preparations. It is also not known whether TRILISATE can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. TRILISATE should be given to a pregnant woman only if clearly needed. Because of the known effects of other salicylate drug products on the fetal cardiovascular system (closure of ductus arteriosus), use during late pregnancy should be avoided.

Labor and Delivery

The effects of TRILISATE on labor and delivery in pregnant women are unknown. Since prolonged gestation and prolonged labor due to prostaglandin inhibition have been reported with the use of other salicylate products, the use of TRILISATE preparations near term is not recommended. Other salicylate products have also been associated with alterations in maternal and neonatal hemostasis mechanisms and with perinatal mortality.

Nursing Mothers

Salicylate is excreted in human milk. Peak milk salicylate levels are delayed, occurring as long as 9 to 12 hours post dose, and the milk: plasma ratio has been reported to be as high as 0.34. Because of the potential for significant salicylate absorption by the nursing infant, caution should be exercised when TRILISATE is administered to a nursing woman.

Pediatric Use

In a four-week, open-label pilot study of patients with juvenile rheumatoid arthritis, children from 6 to 16 years of age previously on aspirin received weight-adjusted doses (50-60 mg/ kg) of TRILISATE 500 mg tablets on a divided b.i.d. schedule with subsequent dose titration to achieve therapeutic serum salicylate levels. Eighty-three percent (83%) of the patients rated the therapeutic effect of TRILISATE as good or excellent. Tinnitus was reported by one patient and elevated SGOT levels at Week 1, which decreased during the trial, were detected in two patients. (See

WARNINGS

Death in adults has been reported following ingestion of doses from 10 to 30 grams of salicylate; however, larger doses have been taken without resulting fatality.

Symptoms

Salicylate intoxication, known as salicylism, may occur with large doses or extended therapy. Common symptoms of salicylism include headache, dizziness, tinnitus, hearing impairment, confusion, drowsiness, sweating, vomiting, diarrhea, and hyperventilation. A more severe degree of salicylate intoxication can lead to CNS disturbances, alteration in electrolyte balance, respiratory and metabolic acidosis, hyperthermia, and dehydration.

Treatment

Reduction of further absorption of salicylate from the gastrointestinal tract can be achieved via emesis, gastric lavage, use of activated charcoal, or a combination of the above. Appropriate I.V. fluids should be administered to correct dehydration, electrolyte imbalance, and acidosis and to maintain adequate renal function. To accelerate salicylate excretion, forced diuresis with alkalinizing solution is recommended. In extreme cases, peritoneal dialysis or hemodialysis should be considered for effective salicylate removal.

Patients who are hypersensitive to non-acetylated salicylates should not take TRILISATE Tablets or Liquid.

TRILISATE Tablets/ Liquid contain salicylate with anti- inflammatory, analgesic and antipyretic action. On ingestion of TRILISATE Tablets/ Liquid, the salicylate moiety is absorbed rapidly and reaches peak blood levels within an average of one to two hours after single doses of the tablets or liquid. The primary route of excretion is renal; the excretion products are chiefly the glycine and glucuronide conjugates. At higher serum salicylate concentrations, the glycine conjugation pathway becomes rapidly saturated. Thus, the slower glucuronide conjugation pathway becomes the rate limiting step for salicylate excretion. In addition, salicylate excreted in the bile as glucuronide conjugate may be reabsorbed. These factors account for the prolongation of salicylate half-life and the nonlinear increase in plasma salicylate level as the salicylate dose is increased. The serum concentration of salicylate is increased by conditions that decrease glomerular filtration rate or proximal tubular secretion.

The bioequivalence of TRILISATE Liquid and Tablets 500 mg/ 750 mg/ 1000 mg has been established. With the tablets, a steady- state condition is usually reached after 4 to 5 doses, and the half- life of elimination, on repeated administration of tablets, is 9 to 17 hours. This permits a maintenance dosage schedule of once or twice daily. Unlike aspirin and certain other non-steroidal anti-inflammatory agents, such as arylpropionic acid derivatives and arylacetic acid derivatives, choline magnesium trisalicylate, at therapeutic dosage levels, does not affect platelet aggregation, as shown by in vitro and in vivo studies.

See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CHOLINE SALICYLATE/MAGNESIUM SALICYLATE - ORAL

(KO-leen sal-ISS-uh-late/mag-NEE-zee-um sal-ISS-uh-late)

COMMON BRAND NAME(S): Trilisate

WARNING: Nonsteroidal anti-inflammatory drugs (including salicylates) may rarely increase the risk for a heart attack or stroke. This effect does not apply to low-dose aspirin. (See Drug Interactions section.) The risk may be greater in people with heart disease or increased risk for heart disease (e.g., due to high blood pressure, diabetes), or with longer use. This drug should not be taken right before or after heart bypass surgery (CABG). Also, this drug may infrequently cause serious (rarely fatal) bleeding from the stomach or intestines. This bleeding can occur without warning symptoms at any time during treatment.

Stop taking this medication and seek immediate medical attention if you notice any of the following rare but very serious side effects: chest pain, severe dizziness, weakness on one side of the body, sudden vision changes, slurred speech, black stools, persistent stomach/abdominal pain, vomit that looks like coffee grounds. (See also Precautions section.)

Talk with your doctor or pharmacist about the risks and benefits of treatment with this medication.

USES: Choline salicylate/magnesium salicylate is used to relieve pain from various conditions. It also reduces pain, swelling, and joint stiffness from arthritis. This medication is known as a nonsteroidal anti-inflammatory drug (NSAID).

HOW TO USE: Take this medication by mouth, usually 2-3 times daily with a full glass of water (8 ounces or 240 milliliters) or as directed by your doctor. Do not lie down for at least 30 minutes after taking this drug. If stomach upset occurs while taking this medication, take it with food, milk, or an antacid. If your doctor directs you to take your dose once daily, it is usually taken at bedtime.

If you are taking the liquid form of this medication, measure the dose carefully using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose. The liquid medication may be mixed with fruit juice just before taking to improve the taste. In this case, drink all of the mixture immediately. Do not prepare a supply for future use.

Dosage is based on your medical condition and response to treatment. Dosage in children may also be based on weight. To reduce your risk of stomach bleeding and other side effects, take this medication at the lowest effective dose for the shortest possible time. Do not increase your dose, take it more frequently, or take it for a longer time than prescribed. For ongoing conditions such as arthritis, continue taking this medication as directed by your doctor. Discuss the risks and benefits with your doctor or pharmacist.

Some medications (e.g., ciprofloxacin, tetracycline) cannot be taken with magnesium. The magnesium in this product may react with these medications, preventing their full absorption. If you are taking medications that cannot be taken with magnesium, take them 2 to 3 hours before or after taking choline salicylate/magnesium salicylate. Ask your pharmacist for more details.

For certain conditions (e.g., arthritis), it may take up to 2 to 3 weeks of taking this drug regularly until you get the full benefit.

If you are taking this drug "as needed" (not on a regular schedule), remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the symptoms have worsened, the medicine may not work as well.

Tell your doctor if your symptoms persist or worsen.

SIDE EFFECTS: Upset stomach, heartburn, nausea, or vomiting may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: dizziness/drowsiness, hearing changes (e.g., ringing in the ears, decreased hearing), stomach pain, swelling of ankles/feet/hands, sudden/unexplained weight gain.

See also Warning section.

Tell your doctor immediately if any of these rare but very serious side effects occur: severe stomach/abdominal pain, easy bruising/bleeding, fast/pounding heartbeat, persistent nausea/vomiting, unusual/extreme tiredness, change in amount/color of urine, yellowing eyes/skin.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice any other side effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking choline salicylate/magnesium salicylate, tell your doctor or pharmacist if you are allergic to it; or to aspirin or other NSAIDs (e.g., ibuprofen, naproxen, salsalate); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: aspirin-sensitive asthma (a history of worsening breathing with runny/stuffy nose after taking aspirin or other NSAIDs), severe kidney disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, bleeding/clotting problems, blood disorders (e.g., anemia), a severe loss of body water (dehydration), kidney disease, liver disease, diabetes, certain genetic conditions (G6PD deficiency, pyruvate kinase deficiency), heart disease (e.g., congestive heart failure, history of heart attack), high blood pressure, growths in the nose (nasal polyps), stomach/intestine/esophagus problems (e.g., bleeding, ulcers, recurring heartburn), stroke, swelling of the ankles/feet/hands.

This medicine may cause stomach bleeding. Daily use of alcohol and tobacco may increase your risk for stomach bleeding, especially when combined with this medicine. Limit alcohol and stop smoking. Consult your doctor or pharmacist for more information.

Before having surgery, tell your doctor or dentist that you are using this medication.

If you have diabetes, this drug may affect your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Promptly report any abnormal results as directed. Your medicine, exercise plan, or diet may need to be adjusted.

Caution is advised when using this drug in the elderly because they may be more sensitive to its side effects, especially stomach bleeding and kidney effects.

This medication is similar to aspirin. Children and teenagers should not take this medication if they have chickenpox, flu, or any undiagnosed illness, or if they have just been given a live virus vaccine, without first consulting a doctor about Reye's syndrome, a rare but serious illness.

During the first 6 months of pregnancy, this medication should be used only when clearly needed. It is not recommended for use during the last 3 months of pregnancy due to possible harm to the unborn baby and problems with normal labor/delivery. Discuss the risks and benefits with your doctor.

This drug may pass into breast milk and could have undesirable effects on a nursing infant. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: cidofovir, ketorolac, flu vaccine given in the nose.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting choline salicylate/magnesium salicylate.

Before using this product, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anabolic steroids (e.g., danazol, oxandrolone), anti-platelet drugs (e.g., clopidogrel), "blood thinners" (e.g., enoxaparin, heparin, warfarin), bisphosphonates taken by mouth (e.g., alendronate), carbonic anhydrase inhibitors (e.g., acetazolamide), certain diabetes drugs (sulfonylureas such as glyburide), certain drugs for seizures (phenytoin, phenobarbital, valproic acid), corticosteroids (e.g., prednisone), cyclosporine, drugs for gout (e.g., probenecid, sulfinpyrazone), drugs for high blood pressure (including ACE inhibitors such as captopril, angiotensin II receptor antagonists such as losartan, and beta blockers such as metoprolol), gabapentin, drugs that affect the acidity of urine (e.g., antacids, citrates, sodium bicarbonate, high doses of vitamin C/ascorbic acid), lithium, other drugs that contain magnesium (e.g., milk of magnesia), methotrexate, pemetrexed, tenofovir, "water pills" (diuretics such as furosemide, hydrochlorothiazide, spironolactone).

Check all prescription and nonprescription medicine labels carefully since many contain pain relievers/fever reducers (NSAIDs such as aspirin, ibuprofen, or naproxen) that are similar to this drug and that may increase your risk for side effects if taken together with this medication. Low-dose aspirin should be continued if prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day). Consult your doctor or pharmacist for more details.

Long-term use of antacids may change how this product works. Ask your doctor or pharmacist about using these products safely.

This medication may interfere with certain laboratory tests (including certain urine glucose tests, thyroid tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: dizziness, ringing in the ears, weakness, drowsiness, fast breathing, confusion, seizures.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., blood pressure, complete blood count, liver and kidney function tests, magnesium levels) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

If you have arthritis, lifestyle changes (e.g., weight loss if needed, strengthening/conditioning exercises) may help improve your flexibility and joint function. Consult your doctor for specific instructions.

MISSED DOSE: If you are taking this drug on a regular schedule (not "as needed") and you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.