Tiaprofenic Acid

Pronunciation

(tye ah PRO fen ik AS id)

Generic Available

Yes

Canadian Brand Names

Albert® Tiafen; Apo-Tiaprofenic®; Dom-Tiaprofenic®; Novo-Tiaprofenic; Nu-Tiaprofenic; PMS-Tiaprofenic; Surgam®; Surgam® SR; Tiaprofenic-200; Tiaprofenic-300

Use

Relief of signs and symptoms of rheumatoid arthritis and osteoarthritis (degenerative joint disease)

Restrictions

Not available in U.S.

Pregnancy Risk Factor

Not assigned; contraindicated (per manufacturer)

Pregnancy Implications

Adequate and well-controlled studies have not been conducted in pregnant women. Fetal exposure to NSAIDs late in pregnancy is associated with premature closure of ductus arteriosus. First trimester miscarriages have been reported.

Lactation

Enters breast milk/not recommended (AAP rates other NSAIDs "compatible")

Contraindications

Hypersensitivity to tiaprofenic acid, any component of the formulation, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs); asthma or nasal polyps; active hepatic disease; renal insufficiency (Clcr<30 mL/minute); active peptic ulcer or active inflammatory disease of gut (diverticulosis, ulcerative colitis, Crohn's disease); pregnancy (3rd trimester)

Warnings/Precautions

Fatal asthmatic and anaphylactoid reactions have occurred in patients with "aspirin triad." Use with caution in patients with CHF, hypertension, dehydration, decreased renal or hepatic function, history of GI disease (bleeding, ulcers, or previous GI symptoms with NSAID use), or those receiving anticoagulants and/or corticosteroids. Use lowest effective dose for shortest period possible; bleeding risk has been correlated to dose and duration of therapy. Gastrointestinal bleeding may occur without prior symptoms of gastrointestinal irritation. Elderly are at a high risk for adverse effects from NSAIDs. As many as 60% of elderly can develop peptic ulceration and/or hemorrhage asymptomatically.

Use of NSAIDs can compromise existing renal function especially when Clcr<30 mL/minute. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high-dose situations; however, elderly may demonstrate these adverse effects at lower doses than younger adults. Withhold for at least 4-6 half-lives prior to surgical or dental procedures.

Patients with autoimmune disorders may be at greater risk of developing aseptic meningitis, as rare adverse reaction associated with some NSAIDs. Avoid use in patients with prior history of urinary symptoms and discontinue at first sign of genitourinary problems. Severe cases of cystitis (bladder pain, dysuria, urinary frequency, hematuria) due to tiaprofenic acid have been reported. Safety and efficacy have not been established in pediatric patients.

Adverse Reactions

1% to 10%:

Cardiovascular: Fluid retention, flushing

Central nervous system: Dizziness, headache, drowsiness, depression

Dermatologic: Rash, pruritus, erythema

Endocrine & metabolic: Hyperkalemia (2%)

Gastrointestinal: Dyspepsia (up to 14%), nausea, heartburn, epigastric distress, vomiting, abdominal pain, constipation, flatulence, diarrhea, stomatitis, xerostomia

Hematologic: Decreased hemoglobin/hematocrit (2.8%)

Renal: Increased BUN (up to 12% in elderly)

<1% (Limited to important or life-threatening): Anaphylaxis, angina, angioedema, asthma, bronchospasm, cystitis, disorientation, duodenal ulcer, dysuria, edema, enterocolitis, erythema multiforme, gastric ulcer, gastrointestinal hemorrhage, hepatotoxicity, hypertension, incontinence, increased serum creatinine, interstitial nephritis, intestinal perforation, melena, menstrual irregularities, paresthesia, photosensitivity, renal failure, Stevens-Johnson syndrome, thrombocytopenia, tinnitus, toxic epidermal necrolysis, urticaria, vaginal bleeding, vertigo. Aseptic meningitis, neutropenia, and leukopenia have been associated rarely with NSAIDs.

Overdosage/Toxicology

Symptoms of overdose include apnea, metabolic acidosis, coma, nystagmus, seizures, leukocytosis, and renal failure. Management of nonsteroidal anti-inflammatory (NSAID) intoxication is supportive and symptomatic. Since many NSAIDs undergo enterohepatic cycling, multiple doses of charcoal may be needed to reduce the potential for delayed toxicities.

Drug Interactions

ACE inhibitors: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure. May precipitate hyperkalemia and renal impairment; monitor potassium and renal function.

Angiotensin II antagonists: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure.

Anticoagulants (warfarin, heparin, LMWHs) in combination with NSAIDs can cause increased risk of bleeding.

Antiplatelet drugs (ticlopidine, clopidogrel, aspirin, abciximab, dipyridamole, eptifibatide, tirofiban) can cause an increased risk of bleeding.

Corticosteroids: May increase the risk of GI ulceration; avoid concurrent use

Cyclosporine: NSAIDs may increase serum creatinine, potassium, blood pressure, and cyclosporine levels; monitor cyclosporine levels and renal function carefully.

Hydralazine's antihypertensive effect is decreased; avoid concurrent use

Lithium levels can be increased; avoid concurrent use if possible or monitor lithium levels and adjust dose. Sulindac may have the least effect. When NSAID is stopped, lithium will need adjustment again.

Loop diuretics efficacy (diuretic and antihypertensive effect) is reduced. Indomethacin reduces this efficacy, however, it may be anticipated with any NSAID.

Methotrexate: Severe bone marrow suppression, aplastic anemia, and GI toxicity have been reported with concomitant NSAID therapy. Avoid use during moderate or high-dose methotrexate (increased and prolonged methotrexate levels). NSAID use during low-dose treatment of rheumatoid arthritis has not been fully evaluated; extreme caution is warranted.

Warfarin's INRs may be increased by piroxicam. Other NSAIDs may have the same effect depending on dose and duration. Monitor INR closely. Use the lowest dose of NSAIDs possible and for the briefest duration. May alter the anticoagulant effects of warfarin; concurrent use with other antiplatelet agents or anticoagulants may increase risk of bleeding.

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).

Food: Tiaprofenic acid peak serum levels may be decreased if taken with food.

Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity).

Stability

Store at 15°C to 30°C (59°F to 86°F).

Mechanism of Action

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors.

Pharmacodynamics/Kinetics

Absorption: Regular release tablet: Rapid

Protein binding: 98%

Metabolism: Minimal (10%) to inactive metabolites

Half-life elimination: 1.7 hours

Time to peak: 30-90 minutes

Excretion: Urine (primarily as unchanged drug)

Dosage

Oral: Adults:

Rheumatoid arthritis:

Tablet: Usual initial and maintenance dose: 600 mg/day in 3 divided doses; some patients may do well on 300 mg twice daily; maximum daily dose: 600 mg

Sustained release capsule: Initial and maintenance dose: 2 sustained release capsules of 300 mg once daily; Surgam® SR capsules should be swallowed whole

Osteoarthritis:

Tablet: Usual initial and maintenance dose: 600 mg/day in 2 or 3 divided doses; in rare instances patients may be maintained on 300 mg/day in divided doses; maximum daily dose: 600 mg

Sustained release capsule: Initial and maintenance dose: 2 sustained release capsules of 300 mg once daily; Surgam® SR capsules should be swallowed whole

Dosage adjustment in renal impairment: No specific dosage adjustment recommended; note caution in renal impairment.

Administration

Administer with food or milk. Capsule should be swallowed whole.

Monitoring Parameters

CBC; occult blood loss and periodic liver function tests; monitor response (pain, range of motion, grip strength, mobility, ADL function), inflammation; observe for weight gain, edema; monitor renal function (urine output, serum BUN, and creatinine); observe for bleeding, bruising; evaluate gastrointestinal effects (abdominal pain, bleeding, dyspepsia); mental confusion, disorientation; with long-term therapy, periodic ophthalmic exams

Dietary Considerations

Should be taken with food or milk.

Patient Education

If self-administered, use exactly as directed; do not increase dose or frequency. Adverse reactions can occur with overuse. Consult your prescriber before use if you have hypertension or heart failure. Take with food or milk. While using this medication, do not use alcohol, other prescription or OTC medications containing aspirin or salicylate, or other NSAIDs without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience nausea, vomiting, gastric discomfort (frequent mouth care, small, frequent meals, chewing gum, sucking lozenges may help). GI bleeding, ulceration, or perforation can occur with or without pain. Stop taking medication and report urinary tract/bladder problems, ringing in ears; persistent cramping or stomach pain; unresolved nausea or vomiting; respiratory difficulty or shortness of breath; unusual bruising or bleeding (mouth, urine, stool); skin rash; unusual swelling of extremities; chest pain; or palpitations. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 3rd trimester of pregnancy. Consult prescriber if breast-feeding.

Additional Information

Not available in U.S.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Dosage Forms

Capsule, sustained release: 300 mg

Tablet: 200 mg, 300 mg

References

Andreassen KH, Eldrup J, Hansen RI, et al, "Tiaprofenic Acid-Induced Cystitis: Three Cases and a Literature Review,"Scand J Urol Nephrol, 1999, 33(6):408-10.

Surgam® prescribing information, Aventis Pharma Inc, Quebec, Revised 1999.

International Brand Names

Albert® Tiafen (CA); Apo-Tiaprofenic® (CA, NZ); Apo-Tiapro® (PL); Artiflam® (BE, LU); Dom-Tiaprofenic® (CA); Fengam® (TH); Flanid® (FR); Novo-Tiaprofenic (CA); Nu-Tiaprofenic (CA); PMS-Tiaprofenic (CA); Surgam® (AU, BE, CA, CH, CZ, DE, EC, FR, GB, HR, HU, ID, IE, LU, MX, NL, NZ, PL, PT, RU, TH, TR, ZA); Surgam® SR (CA); Surgamyl® (DK, FI, IT); Tiaprofenic-200 (CA); Tiaprofenic-300 (CA); Tiaprofenic Acid® (GB); Tiaprofen® (IT); Turganil® (YU)