Diclofenac and Misoprostol

Pronunciation

(dye KLOE fen ak & mye soe PROST ole)

U.S. Brand Names

Arthrotec®

Synonyms

Misoprostol and Diclofenac

Generic Available

Canadian Brand Names

Arthrotec®

Use

The diclofenac component is indicated for the treatment of osteoarthritis and rheumatoid arthritis; the misoprostol component is indicated for the prophylaxis of NSAID-induced gastric and duodenal ulceration

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

Enters breast milk/contraindicated

Contraindications

Hypersensitivity to diclofenac, aspirin, other NSAIDs, misoprostol, other prostaglandins, or any component of the drug product; pregnancy

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

Also see individual agents.

>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

Diclofenac: Substrate (minor) of CYP1A2, 2B6, 2C8/9, 2C19, 2D6, 3A4; Inhibits CYP1A2 (moderate), 2C8/9 (weak), 2E1 (weak), 3A4 (strong)

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

See individual agents.

Pharmacodynamics/Kinetics

See individual agents.

Dosage

Oral:

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

See individual agents. Consult your prescriber before use if you have hypertension or heart failure. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate contraceptive measures. The misoprostol ingredient in this drug may cause severe fetal defects, miscarriage, or abortion; do not share medication with others. Do not breast-feed.

Cardiovascular Considerations

In short-term use, NSAIDs vary considerably in their effect on blood pressure. A recent meta-analysis (see references) showed that indomethacin and naproxen had the largest effect on blood pressure. Other NSAIDs, including piroxicam, ibuprofen, and sulindac had less of an effect. Ibuprofen combined with captopril or losartan may attenuate the antihypertensive effects of ACE inhibition or receptor blockade on sitting or 24-hour ambulatory diastolic blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short. The use of NSAIDs in the treatment of patients with congestive heart failure may be associated with an increased risk for fluid accumulation and edema. One study showed that NSAID use in elderly patients had an increased risk of hospitalization for heart failure. This study gives compelling reasons to avoid or limit the use of NSAIDs in patients with congestive heart failure, particularly in the elderly population.

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

Mental Health: Effects on Mental Status

May cause nervousness or dizziness; may rarely cause depression

Mental Health: Effects on Psychiatric Treatment

May rarely cause may agranulocytosis; use caution with clozapine and carbamazepine; may decrease the clearance of lithium resulting in elevated serum levels and potential toxicity; monitor serum lithium levels

Dosage Forms

Tablet: Diclofenac sodium 50 mg and misoprostol 200 mcg; diclofenac sodium 75 mg and misoprostol 200 mcg

References

Conlin P, Moore T, Swartz S, et al, "Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients," Hypertension , 2000, 36(3):461-5.

Morgan TO, Anderson A, and Bertram D, "Effect of Indomethacin on Blood Pressure in Elderly People With Essential Hypertension Well Controlled on Amlodipine or Enalapril," Am J Hypertens , 2000, 13(11):1161-7.

International Brand Names

Arthrotec® (CA)

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

Home > Medical Reference > Complementary Medicine