Pronunciation:

(dye KLOE fen ak & mye soe PROST ole)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Based on diclofenac component: Safety and efficacy in pregnant women have not been established. Exposure late in pregnancy may lead to premature closure of the ductus arteriosus and may inhibit uterine contractions.

Based on misoprostol component: Misoprostol is an abortifacient. Administration by any route is contraindicated in pregnancy. Reports of fetal death and congenital anomalies have been received after the use of misoprostol as an abortifacient.

Lactation:

Contraindications:

Warnings/Precautions:

Based on diclofenac component: 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.

Rare cases of severe hepatic reactions (including necrosis, jaundice, fulminant hepatitis) have been reported. Vision changes (including changes in color) have been rarely reported with oral diclofenac.

Based on misoprostol component: Safety and efficacy have not been established in children <18 years of age; use with caution in patients with renal impairment and the elderly; not to be used in pregnant women or women of childbearing potential unless woman is capable of complying with effective contraceptive measures; therapy is normally begun on the second or third day of next normal menstrual period. Uterine perforation and/or rupture have been reported in association with intravaginal use to induce labor or with combined oral/intravaginal use to induce abortion. Should not be used as a cervical-ripening agent for induction of labor or termination of pregnancy.

Adverse Reactions:

>10%: Gastrointestinal: Abdominal pain (21%), diarrhea (19%), nausea (11%), dyspepsia (14%)

1% to 10%:

Endocrine & metabolic: Transaminases increased

Gastrointestinal: Flatulence (9%)

Hematologic: Anemia

Miscellaneous: Anaphylactic reactions

Postmarketing and/or case reports (associated with misoprostol): Uterine rupture, fetal or infant death (when used during pregnancy)

Drug Interactions:

Increased effect/toxicity: Aspirin (shared toxicity), digoxin (elevated digoxin levels), warfarin (synergistic bleeding potential), cyclosporine (increased nephrotoxicity), lithium (increased lithium levels)

Decreased effects: Aspirin (displaces diclofenac from binding sites), antihypertensive agents (decreased blood pressure control), antacids (may decrease absorption)

ACE inhibitors: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure

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

CYP1A2 substrates: Diclofenac may increase the levels/effects of CYP1A2 substrates. Example substrates include aminophylline, fluvoxamine, mexiletine, mirtazapine, ropinirole, theophylline, and trifluoperazine.

CYP3A4 substrates: Diclofenac may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam), cisapride, ergot alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and simvastatin), and pimozide are generally contraindicated with strong CYP3A4 inhibitors.

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.

Mechanism of Action:

Pharmacodynamics/Kinetics:

Dosage:

Adults:

Arthrotec® 50:

Osteoarthritis: 1 tablet 2-3 times/day

Rheumatoid arthritis: 1 tablet 3-4 times/day

For both regimens, if not tolerated by patient, the dose may be reduced to 1 tablet twice daily

Arthrotec® 75:

Patients who cannot tolerate full daily Arthrotec® 50 regimens: 1 tablet twice daily

Note: The use of these tablets may not be as effective at preventing GI ulceration

Elderly: No specific dosage adjustment is recommended; may require reduced dosage due to lower body weight; monitor renal function

Patient Education:

Cardiovascular Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

International Brand Names: