Keith, my feeling is, the more I become familiar with trilisate, the more I like it. Of course, I’d really prefer to have more clinical experience with it, and I have not yet gotten a price, but it seems, on paper, to be a good drug. My pain management attending is a big fan of it.

Jonnathan

Summary:

Trilisate:

Advantages:

1. Less GI effects

2. Less hematologic effects

3. Less renal effects

4. Can be used in patients with AIA

5. Can be dosed QD

6. Can be used in children

7. With usual caveats, equally efficacious with other NSAIDS

8. At prescription level, less expensive than naproxyn sodium.

Disadvantages:

1. By script only

2. Unfamiliar to many

3. /s heme side effects, could not be used to sustain an MI pt in lieu of ASA / continuous dose other NSAIDS.

Here is the literature to back this up:

Description:

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.

Pharmacokinetics:

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

Indications and Usage

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.

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 generation1-7, the potential exists for increased levels of unbound warfarin with their concurrent use.

In recommendations for managemetn of osteaaorthritic pain, lternative NSAIDs with fewer gastrointestinal effects, such as choline magnesium trisalicylate, or the addition of misoprostol should be considered to reduce the risk of gastric toxicity. Acetaminophen and the nonacetylated salicylates such as salsalate (Disalcid), sodium salicylate, and choline magnesium trisalicylate (Trilisate) do not affect platelet function and do not alter bleeding times. Other NSAIDs produce a reversible platelet inhibition. With the exception of acetaminophen and the nonacetylated salicylates, NSAIDs should be avoided in patients who are thrombocytopenic, have a bleeding disorder, or are at risk for falls or other injuries¹³.

Use of TRILISATE Liquid is appropriate when a liquid dosage form is preferred,

as in the elderly patient.

Analgesic and Antipyretic Action:

TRILISATE Tablets/Liquid are also indicated for the relief of mild to moderate pain and for antipyresis.

Pediatric Use: In children, TRILISATE preparations are indicated for conditions requiring anti-inflammatory or analgesic action--such as juvenile rheumatoid arthritis and other appropriate conditions. 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.

Patients with ASA Induced Asthma can also safely receive sodium salicylate, salicylamide, choline magnesium trisalicylate, benzydamine, chloroquine, azapropazone, and dextropropoxyphen. These drugs are devoid of anti-COX activity or are weak COX-2 inhibitors¹⁶.

Contraindications:

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

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 studies¹. 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.

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.

Comparative efficacy:

Naproxen in average doses of 643 mg daily was reported as effective as choline magnesium trisalicylate 2466 mg daily in the treatment of rheumatoid arthritis in a double-blind, 12-week multicenter clinical trial involving 114 ambulatory outpatients. Adverse effects occurred more frequently in naproxen treated patients (24%) as compared to choline magnesium trisalicylate patients (15%), with gastrointestinal symptoms predominating⁹.

In addition to aspirin, ibuprofen, and naproxen, which are currently available over-the-counter, more than a dozen prescription NSAIDs are available in the United States. They are approximately equal in efficacy, although there is generally great variability in patients' responses. Toxicities appear to be comparable as well, although nonacetylated salicylates (e.g., choline magnesium trisalicylate, salsalate) have less renal toxicity and antiplatelet effects ¹⁵.

Pricing:

For 750 mg BID, 60 pills would cost $24.71. For equianlgesic naproxyn sodium (500 mg bid), 60 pills would cost $26.40 (generics on both meds)¹⁷.

Dosage:

Generic names Trade names Tablet size (mg) Starting dose (mg) Dose interval

Choline a Trilisate 500, 750, 1000 1000-1500 bid

Magnesium

Trisalicylate b

a Nonacetylated salicylates.

b Available in liquid or suspension form¹⁴.

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 patient's response. In patients with renal dysfunction, monitor salicylate levels and adjust dose accordingly.

ELDERLY: In the elderly patients, 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 patient's 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 gr of aspirin; each 750 mg tablet, to 15 gr of aspirin; and each 1000 mg tablet, to 20 gr 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.

Weight (kg)

Total daily dose

12-13

500 mg

14-17

750 mg

18-22

1000 mg

23-27

1250 mg

28-32

1500 mg

33-37

1750 mg

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 swallow a solid dosage form.

Citations

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; Pharma-therapeutica; 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 et al; 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 evaluation 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; Rheumatology and Rehabilitation; 19:30-41, 1980.

11.Goldenberg, A; Rudnicki, RD, and Koonce, ML; Clinical comparison 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.

15. Furst DE: Are there differences among nonsteroidal antiinflammatory drugs? Comparing acetylated salicylates, nonacetylated sailcylates, and nonacetylated nonsteroidal antiinflammatory drugs. Arthritis Rheum 37:1-9, 1994

16.Szczeklik A, Stevenson DD. Current reviews of allergy and clinical immunology. Aspirin-induced asthma: Advances in pathogenesis and management Journal of Allergy and Clinical Immunology Volume 104 • Number 1 • July 1999

17.Rite Aid Pharmacy. Personal discussion with pharmacist. Pittsburgh, PA: 9/7/99.