Tolectin

SIDE EFFECTS

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

Read the Tolectin (tolmetin sodium) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

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%.

Read the Tolectin Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 2/11/2008
This monograph has been modified to include the generic and brand name in many instances.

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