TOLECTIN 600
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TOLECTIN 600 (TOLECTIN 600).
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis.
| Metabolism | Hepatic metabolism primarily via CYP2C9 and CYP2C8; forms inactive metabolites. |
| Excretion | Renal: approximately 90% as metabolites and conjugates; biliary/fecal: minor (less than 10%) |
| Half-life | Terminal elimination half-life is approximately 5 hours (range 4-6 hours) in healthy adults; prolonged in renal impairment. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.15-0.2 L/kg; indicates distribution mainly into extracellular fluid. |
| Bioavailability | Oral: approximately 90-100% (well absorbed with minimal first-pass metabolism). |
| Onset of Action | Oral: 30-60 minutes for analgesic effect. |
| Duration of Action | Oral: 4-6 hours (analgesic); anti-inflammatory effect may persist longer with repeated dosing. |
600 mg orally three times daily; maximum 1800 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR < 10-30 mL/min: cautious use, reduce dose by 50% if necessary; GFR < 10 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for children under 18 years of age. |
| Geriatric use | Start at lower end of dosing range, consider 400 mg three times daily, monitor renal function and gastrointestinal tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TOLECTIN 600 (TOLECTIN 600).
| Breastfeeding | Excreted into human milk in low amounts; M/P ratio not established. Due to potential adverse effects on infant renal function and cardiovascular system, breastfeeding is not recommended, especially with prolonged use. |
| Teratogenic Risk | Pregnancy Category C (pre-2015) for NSAIDs; Category D from 30 weeks gestation onward. First trimester: possible increased risk of miscarriage and cardiac defects. Second trimester: avoid prolonged use due to risk of oligohydramnios. Third trimester: contraindicated due to risk of premature ductus arteriosus closure and persistent pulmonary hypertension in the neonate. |
■ FDA Black Box Warning
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
History of hypersensitivity to tolmetin or other NSAIDs; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in the setting of CABG surgery; advanced renal disease; active GI bleeding or ulcer disease.
| Precautions | Cardiovascular risk (including MI and stroke); gastrointestinal risk (bleeding, ulceration, perforation); renal toxicity (including papillary necrosis and renal failure); hepatic toxicity; anaphylactoid reactions; elevated liver enzymes; anemia; fluid retention and edema; hypertension. |
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| Fetal Monitoring | Monitor amniotic fluid volume via ultrasound if prolonged use; fetal echocardiography in third trimester if exposure occurs; assess for ductus arteriosus constriction. Monitor maternal renal function, blood pressure, and signs of bleeding. |
| Fertility Effects | May impair female fertility by interfering with ovulation via prostaglandin synthesis inhibition; effects are reversible upon discontinuation. No known effects on male fertility. |