Dosing and uses of Tolectin (tolmetin)
Adult dosage forms and strengths
tablet
- 200mg
- 600mg
capsule
- 400mg
Osteoarthritis
200-600 mg PO q8hr
Not to exceed 1800 mg/day
Rheumatoid Arthritis
200-600 mg PO q8hr
Not to exceed 1800 mg/day
Administration
Take with 8-12 oz water to avoid GI effects
Other Indications & Uses
Pain, juvenile rheumatoid arthritis
Pediatric dosage forms and strengths
tablet
- 200mg
- 600mg
capsule
- 400mg
Juvenile Idiopathic Arthritis
<2 years
- Safety and efficacy not established
>2 Years
- Initial: 20-30 mg/kg/day PO divided q6-8hr
- Maintenance: 15-30 mg/kg/day divided q6-8hr
Analgesic (Unlabeled)
20-28 mg/kg/day PO divided q6hr
Administration
Take with 8-12 oz water to avoid GI effects
Tolectin (tolmetin) adverse (side) effects
>10%
Increased liver function test (up to 15%)
1-10%
Nausea (10%)
Hypertension (3-9%)
Myocardial infarction (<2%)
Edema
Weight gain, Weight loss
Abdominal pain
Diarrhea
Flatulence
Indigestion
Nausea, Vomiting
Asthenia
Dizziness
Headache
<1%
Thrombotic tendency observations
Erythema multiforme
Scaling eczema
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Gastrointestinal hemorrhage
Gastrointestinal perforation
Inflammatory disorder of digestive tract
Agranulocytosis
Anemia
Neutropenia
Thrombocytopenia
Jaundice
Liver failure
Anaphylactoid reaction
Cerebrovascular accident
Acute renal failure
Hematuria
Proteinuria
Bronchospasm
Warnings
Black box warnings
Cardiovascular Risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), & stroke, which can be fatal
- Risk may increase with duration of use
- Patients with risk factors for or existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke)
Gastrointestinal Risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, & perforation of the stomach or intestines, which can be fatal
- GI adverse events may occur at any time during use & without warning symptoms
- Elderly patients are at greater risk for serious GI events
Contraindications
Absolute: ASA allergy, hepatic disease (severe chronic), hepatitis, jaundice, nursing mother
Relative: Bleeding disorder, duodenal/gastric/peptic ulcer, stomatitis, SLE, ulcerative colitis, upper GI disease, late pregnancy (may cause premature closure of ductus arteriosus)
Cautions
Use caution in asthma (bronchial), cardiac disease, CHF, hepatic impairment, HTN, renal impairment
Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs
Strong cross-sensitivity may exist for ASA allergic patients
Food reduces bioavailability
Heart Failure(HF) risk
- NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
- NSAIDS should be avoided or withdrawn whenever possible
- AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134
Pregnancy and lactation
Pregnancy category: C; avoid in late pregnancy, may cause premature closure of ductus arteriosus
The Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and in approximately 2.6% of controls. (CMAJ, September 6, 2011; DOI:10.1503/cmaj.110454)
Lactation: excreted in breast milk; safety in nursing infants not known
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tolectin (tolmetin)
Mechanism of action
Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2).
May inhibit chemotaxis, may alter lymphocyte activity, decrease proinflammatory cytokine activity, and may inhibit neutrophil aggregation. These effects may contribute to its anti-inflammatory activity.
Pharmacokinetics
Peak Plasma Time: 30-60 min
Concentration: 40 mcg/mL
Onset of action: 1-2hr
Half-life elimination: 1 hr
Protein Bound: 99%
Vd: 9.1 L
Metabolism: Liver oxidation
Metabolites: Dicarboxylic acid metabolite
Excretion: Urine (approx 100%)
Enzymes inhibited: Cyclooxygenase
