Side Effects of Tolectin (tolmetin)

Tolectin (tolmetin) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat fever, as well as pain and inflammation that results from rheumatoid arthritis, juvenile arthritis, or osteoarthritis. 

As a group, NSAIDs are non-narcotic relievers of mild to moderate pain of many causes, including injury, menstrual cramps, arthritis, and other musculoskeletal conditions. They work by reducing the levels of prostaglandins, chemicals responsible for pain, fever, and inflammation. 

Tolectin blocks the enzyme that makes prostaglandins (cyclooxygenase), resulting in lower concentrations of prostaglandins. As a consequence, inflammation, pain and fever are reduced. The brand name Tolectin is discontinued. 

Common side effects of Tolectin include:

• gastrointestinal ulcerations,
• abdominal pain,
• cramping,
• nausea,
• gastritis,
• serious gastrointestinal bleeding,
• liver toxicity,
• stomach ulceration,
• black tarry stools, and
• weakness.

Serious side effects of Tolectin include:

• heart attacks,
• strokes,
• accumulation of fluid,
• increased chance of heart failure, and
• it may cause or worsen high blood pressure and kidney failure.

Drug interactions of Tolectin include blood thinning medications (anticoagulants) because of an increased risk of bleeding. 

Tolectin may inhibit the elimination of lithium or methotrexate from the body and can result in toxic blood levels of either drug. 

Side effects from cyclosporine may be increased by Tolectin. 

Tolmetin may reduce the effectiveness of antihypertensives. 

Combining Tolectin with angiotensin receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors in patients who are elderly, volume-depleted (including those on diuretic therapy), or with poor kidney function may result in reduced kidney function, including kidney failure. 

Consuming more than three alcoholic beverages per day while using Tolectin increases the risk of developing stomach ulcers. 

Tolectin is generally avoided during pregnancy. Tolectin is excreted in breast milk. To avoid adverse effects in the infant, nursing mothers should decide whether to stop breastfeeding or stop Tolectin.

Most patients benefit from tolmetin and other NSAIDs with few side effects. However, serious side effects can occur, and generally tend to be dose related. Therefore, it is advisable to use the lowest effective dose to minimize side effects. The most common side effects of tolmetin involve the gastrointestinal system, and these include:

• ulcerations,
• abdominal pain,
• cramping,
• nausea,
• gastritis,
• serious gastrointestinal bleeding,
• liver toxicity,
• stomach ulceration
• black tarry stools, and
• weakness.

Tolmetin should be avoided by patients with a history of asthma, hives, or other allergic reactions to aspirin or other NSAIDs. Rare but severe allergic reactions have been reported in such individuals. It also should be avoided by patients with peptic ulcer disease or poor kidney function, since this medication can aggravate both conditions.

Other important side effects include:

• heart attacks
• strokes
• accumulation of fluid, and
• increased chance ofheart failure.

Tolmetin may cause or worsen high blood pressure and kidney failure.

The adverse reactions which have been observed in clinical trials encompass observations in about 4370 patients treated with Tolectin (tolmetin sodium), over 800 of whom have undergone at least one year of therapy. These adverse reactions, reported below by body system, are among those typical of nonsteroidal anti- inflammatory drugs and, as expected, gastrointestinal complaints were most frequent. In clinical trials with Tolectin (tolmetin sodium) , about 10% of patients dropped out because of adverse reactions, mostly gastrointestinal in nature.

Incidence Greater Than 1%

The following adverse reactions which occurred more frequently than 1 in 100 were reported in controlled clinical trials.

Gastrointestinal: Nausea (11%), dyspepsia,* gastrointestinal distress,* abdominal pain,* diarrhea,* flatulence,* vomiting,* constipation, gastritis, and peptic ulcer. Forty percent of the ulcer patients had a prior history of peptic ulcer disease and/or were receiving concomitant anti- inflammatory drugs including corticosteroids, which are known to produce peptic ulceration.

Body as a Whole: Headache, * asthenia, * chest pain

Cardiovascular: Elevated blood pressure, * edema*

Central Nervous System: Dizziness, * drowsiness, depression

Metabolic/Nutritional: Weight gain, * weight loss*

Dermatologic: Skin irritation

Special Senses: Tinnitus, visual disturbance

Hematologic: Small and transient decreases in hemoglobin and hematocrit not associated with gastrointestinal bleeding have occurred. These are similar to changes reported with other nonsteroidal anti- inflammatory drugs.

Urogenital: Elevated BUN, urinary tract infection

*Reactions occurring in 3% to 9% of patients treated with Tolectin (tolmetin sodium) . Reactions occurring in fewer than 3% of the patients are unmarked.

Incidence Less Than 1%

(Causal Relationship Probable)

The following adverse reactions were reported less frequently than 1 in 100 controlled clinical trials or were reported since marketing. The probability exists that there is a causal relationship between Tolectin (tolmetin sodium) and these adverse reactions.

Gastrointestinal: Gastrointestinal bleeding with or without evidence of peptic ulcer, perforation, glossitis, stomatitis, hepatitis, liver function abnormalities.

Body as a Whole: Anaphylactoid reactions, fever, lymphadenopathy, serum sickness

Hematologic: Hemolytic anemia, thrombocytopenia, granulocytopenia, agranulocytosis

Cardiovascular: Congestive heart failure in patients with marginal cardiac function.

Dermatologic: Urticaria, purpura, erythema multiforme, toxic epidermal necrolysis

Urogenital: Hematuria, proteinuria, dysuria, renal failure

Incidence Less Than 1%

(Causal Relationship Unknown)

Other adverse reactions were reported less frequently than 1 in 100 in controlled clinical trials or were reported since marketing, but a causal relationship between Tolectin (tolmetin sodium) and the reaction could not be determined. These rarely reported reactions are being listed as alerting information for the physician since the possibility of a causal relationship cannot be excluded.

Body as a Whole: Epistaxis

Special Senses: Optic neuropathy, retinal and macular changes

ACE-inhibitors

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE- inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE- inhibitors.

Aspirin

As with other NSAIDs, concomitant administration of tolmetin sodium and aspirin is not generally recommended because of the potential of increased adverse effects.

Diuretics

Clinical studies, as well as post- marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy.

Lithium

NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.

Methotrexate

NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.

Warfarin

The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.

The in vitro binding of warfarin to human plasma proteins is unaffected by tolmetin, and tolmetin does not alter the prothrombin time of normal volunteers. However, increased prothrombin time and bleeding have been reported in patients on concomitant Tolectin (tolmetin sodium) and warfarin therapy. Therefore, caution should be exercised when administering Tolectin (tolmetin sodium) to patients on anticoagulants.

Hypoglycemic Agents

In adult diabetic patients under treatment with either sulfonylureas or insulin there is no change in the clinical effects of either Tolectin (tolmetin sodium) or the hypoglycemic agents.

Drug/Laboratory Test Interactions

The metabolites of tolmetin sodium in urine have been found to give positive tests for proteinuria using tests which rely on acid precipitation as their endpoint (e.g., sulfosalicylic acid). No interference is seen in the tests for proteinuria using dye- impregnated commercially available reagent strips (e.g., Albustix, Uristix, etc.).

Drug-Food Interactions

In a controlled single-dose study, administration of Tolectin (tolmetin sodium) with milk had no effect on peak plasma tolmetin concentrations, but decreased total tolmetin bioavailability by 16%. When Tolectin (tolmetin sodium) was taken immediately after a meal, peak plasma tolmetin concentrations were reduced by 50% while total bioavailability was again decreased by 16%.