Usual Adult Dose for Osteoarthritis

One tablet (diclofenac 50 mg-misoprostol 200 mcg) orally 3 times a day
Maximum doses: diclofenac 150 mg/day; misoprostol 200 mcg/dose and 800 mcg/day

Comments:

• Monitor response to initial therapy and adjust dose and frequency to fit individual needs; consider titration of individual components if appropriate.
• For patients who experience intolerance, diclofenac 75 mg-misoprostol 200 mcg or diclofenac 50 mg-misoprostol 200 mcg orally twice a day may be used, however these regimens are less effective in preventing ulcers.
• For gastric ulcer prevention, misoprostol 200 mcg 3 times a day is therapeutically equivalent to 200 mcg 4 times a day and both are more protective than 200 mcg 2 times a day.
• For duodenal ulcer prevention, misoprostol 200 mcg 4 times a day is more protective than 200 mcg 2 or 3 times a day, but may not be well tolerated.

Use: For the treatment of signs and symptoms of osteoarthritis in patients at high risk of developing nonsteroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers and their complications

Usual Adult Dose for Rheumatoid Arthritis

One tablet (diclofenac 50 mg-misoprostol 200 mcg) orally 3 to 4 times a day
Maximum doses: diclofenac 225 mg/day; misoprostol 200 mcg/dose and 800 mcg/day

Comments:

• For patients who experience intolerance, diclofenac 75 mg-misoprostol 200 mcg or diclofenac 50 mg-misoprostol 200 mcg orally twice a day may be used, however these regimens are less effective in preventing ulcers.
• Monitor response to initial therapy and adjust dose and frequency to fit individual needs; consider titration of individual components if appropriate.
• For gastric ulcer prevention, misoprostol 200 mcg 3 times a day is therapeutically equivalent to 200 mcg 4 times a day and both are more protective than 200 mcg 2 times a day.
• For duodenal ulcer prevention, misoprostol 200 mcg 4 times a day is more protective than 200 mcg 2 or 3 times a day, but may not be well tolerated.

Use: For the treatment of signs and symptoms of rheumatoid arthritis in patients at high risk of developing NSAID induced gastric and duodenal ulcers and their complications

Renal Dose Adjustments

Use with caution in patients with advanced renal disease; if treatment is initiated, close monitoring of renal function is recommended.

Liver Dose Adjustments

Use with caution.

• Avoid use in patients with hepatic porphyria

Dose Adjustments

This drug should be used at the lowest effective dose in order to achieve therapeutic efficacy and minimize adverse effects; however, this fixed combination product is not recommended for patients who would not receive the appropriate dose of both ingredients.

For patients who experience intolerance: Diclofenac 75 mg-misoprostol 200 mcg or diclofenac 50 mg-misoprostol 200 mcg orally twice a day may be used, however these regimens are less effective in preventing ulcers.

Concomitant use of CYP450 2C9 inhibitors: Total daily dose of diclofenac should not exceed the lowest recommended dose of 50 mg twice a day

Precautions

US BOXED WARNINGS:

• PREGNANCY: Administration of misoprostol to women who are pregnant can cause abortion, premature birth, birth defects or uterine rupture. Uterine rupture has been reported when misoprostol was administered in pregnant women to induce labor or to induce abortion; uterine rupture risk increases with advancing gestational age and prior uterine surgery including caesarian delivery. This drug should not be taken by pregnant women.
• Patients must be advised of the abortifacient property and warned not to give the drug to others. It should not be used in women of childbearing potential unless the patient requires nonsteroidal anti-inflammatory drug (NSAID) therapy and is at high risk of developing gastric or duodenal ulceration or for developing complications from gastric or duodenal ulcers associated with the use of the NSAID. In such patients, this drug may be prescribed if:
• a negative serum pregnancy test is obtained within 2 weeks prior to beginning therapy
• the patient is capable of complying with effective contraceptive measures
• the patient has received both oral and written warnings of the hazards of misoprostol, the risk of possible contraception failure, and the danger if this drug should be taken by other women of childbearing potential
• this drug will be started on the second or third day of the next normal menstrual period
• CARDIOVASCULAR THROMBOTIC EVENTS: NSAIDs cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and increase with duration of use. This drug is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
• GASTROINTESTINAL (GI) BLEEDING, ULCERATION, AND PERFORATION: NSAIDs cause an increased risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Swallow whole; do not chew, crush, or dissolve tablets
• Take with food
• Avoid magnesium-containing antacids to minimize the possibility of diarrhea

General:

• Prior to initiating treatment, the potential benefits and risks of using this drug should be weighed against other treatment options.
• Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Monitoring:

• Blood pressure should be monitored closely during initiation and throughout course of therapy.
• Monitor for signs/symptoms of gastrointestinal bleeding.
• Closely monitor renal status, especially in patients with conditions where renal prostaglandins have a supportive role in the maintenance of renal perfusion.
• Monitor transaminases within 4 to 8 weeks of starting therapy
• Periodically monitor blood counts, renal and hepatic function in patients on long-term therapy.

Patient advice:

• This drug may cause gastrointestinal discomfort, especially in the first few weeks; if there is prolonged difficulty, or severe diarrhea, cramping, and/or nausea, instruct the patient to contact their health care provider.
• Patients should seek medical advice for signs and symptoms of cardiovascular effects, gastrointestinal events, adverse skin reactions, allergic reactions, hepatotoxicity, or unexplained weight gain or edema.
• Patients should talk to their health care provider if they are pregnant, planning on becoming pregnant, or breastfeeding; patients should be instructed on the abortifacient properties of this drug and warned not to give this drug to others, especially women of childbearing potential.
• Patients should talk to their health care provider before they use over the counter analgesics.