Side Effects of Trilisate (choline magnesium salicylate or trisalicylate)

Trilisate (choline magnesium salicylate or trisalicylate) is a nonsteroidal anti-inflammatory drug (NSAID), referred to as a salicylate, effective in treating fever, pain, and inflammation in the body caused by soft tissue injuries, tendinitis, bursitis, and arthritic conditions. 

It works by reducing the levels of prostaglandins, chemicals that are responsible for pain, fever, and inflammation. The salicylates block the enzyme that makes prostaglandins (cyclooxygenase), resulting in lower concentrations of prostaglandins. As a consequence, inflammation, pain and fever are reduced. The brand name Trilisate is no longer available in the U.S.

Common side effects of Trilisate include

• heartburn,
• stomach ulcers,
• nausea, and
• vomiting. 

Serious side effects of Trilisate include

• severe abdominal pain,
• easy bruising or bleeding,
• fast heartbeat,
• persistent nausea or vomiting,
• unusual tiredness,
• change in the amount or color of urine,
• yellowing of the eyes or skin (jaundice),
• unusual bleeding, and
• hearing loss.

Drug interactions of Trilisate include methotrexate because the blood levels of methotrexate may increase, presumably because the elimination of methotrexate from the body is reduced. This may lead to more methotrexate-related side effects.

• Concurrent use of Trilisate and warfarin may cause excessive bleeding as Trilisate enhances the effect of warfarin. It is therefore important to reduce the dosage of warfarin. NSAIDs may reduce the blood pressure-lowering effects of drugs that are given to reduce blood pressure. This may occur because prostaglandins play a role in the regulation of blood pressure.
• Persons who have more than three alcoholic beverages per day may be at increased risk of developing stomach ulcers when taking Trilisate or other NSAIDs.
• Trilisate, as other salicylates, should not be given within six weeks of influenza virus vaccine as this can increase risk of Reye's syndrome (a serious, often fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver) due to unknown mechanisms. 

It is also unknown if 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. 

Trilisate is excreted in breast milk; therefore, caution should be exercised when administering it to breastfeeding women.

Common side effects of choline magnesium salicylate are

• heartburn,
• stomach ulcers,
• nausea, or
• vomiting.

Patients should tell their doctor immediately if any of these unusual but potentially serious side effects occur:

• severe abdominal pain,
• easy bruising or bleeding,
• fast heartbeat,
• persistent nausea or vomiting,
• unusual tiredness,
• change in the amount or color of urine,
• yellowing of the eyes or skin,
• unusual bleeding, and
• hearing loss.

The most frequent adverse reactions observed with Trilisate (choline magnesium trisalicylate) 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 have not been reported with Trilisate (choline magnesium trisalicylate) 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 (choline magnesium trisalicylate) 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 (choline magnesium trisalicylate) preparations is initiated.
• The effect of Trilisate (choline magnesium trisalicylate) 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 (choline magnesium trisalicylate) 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.