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Diclofenac and Misoprostol (Systemic)


VA CLASSIFICATION
Primary: MS109

Commonly used brand name(s): Arthrotec 50; Arthrotec 75.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antirheumatic (nonsteroidal anti-inflammatory)—

Indications

Accepted

Arthritis, rheumatoid (treatment) or
Osteoarthritis (treatment)—Diclofenac and misoprostol combination is indicated for treatment of the signs and symptoms of rheumatoid arthritis and osteoarthritis in patients at high risk of developing nonsteroidal anti-inflammatory drug (NSAID)–induced gastric and duodenal ulcers {01}{02}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Diclofenac sodium: 318.14 {01}
    Misoprostol: 382.54 {01}

Mechanism of action/Effect:

Diclofenac—Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) {01}. Results of pharmacological studies show that diclofenac has anti-inflammatory, analgesic, and antipyretic therapeutic effects {01}. The exact mechanism of action has not been determined but may be related to its inhibitory effect on prostaglandin synthesis {01}. A deficiency of prostaglandins within the gastric and duodenal mucosa may lead to a decrease in bicarbonate and mucus secretion, resulting in possible mucosal damage caused by NSAIDs {01}.


Misoprostol:


Cytoprotective—

Misoprostol enhances natural gastromucosal defense mechanisms and healing in acid-related disorders, probably by increasing production of gastric mucus and mucosal secretion of bicarbonate {01}.



Antisecretory—

Misoprostol inhibits basal and nocturnal gastric acid secretion by direct action on parietal cells; also inhibits gastric acid secretion stimulated by coffee, food, histamine, and pentagastrin {01}. It decreases pepsin secretion under basal, but not histamine, stimulation {01}. Misoprostol has no significant effect on fasting or postprandial gastrin or intrinsic factor output {01}.



Absorption:

Diclofenac—Rapidly absorbed following oral administration {01}.

Misoprostol—Rapidly absorbed following oral administration {01}.

Following oral administration of diclofenac and misoprostol combination (50 mg/200 mcg and 75 mg/200 mcg doses, respectively), a similar rate and extent of absorption for diclofenac and misoprostol administered alone were observed {01}. Food decreases the bioavailability of the combination of diclofenac and misoprostol {01}.

Distribution:

Volume of distribution (Vol D)—steady-state:

Diclofenac—550 mL per kg of body weight (mL/kg){01}.

Protein binding:

Diclofenac—Very high (99%) {01}.

Misoprostol acid (active metabolite)—High (< 90%) {01}.

Biotransformation:

Diclofenac—Hepatic; almost 50% eliminated via first-pass metabolism; some active metabolites {01}.

Misoprostol—Rapidly de-esterfied to misoprostol acid (primary biologically active metabolite) {01}.

Half-life:


Elimination:

Diclofenac: 120 minutes {01}.

Misoprostol acid metabolite: Approximately 30 minutes {01}.


Onset of action:

Misoprostol—Within 30 minutes {01}.

Time to peak concentration:

Diclofenac—2 hours {01}.

Misoprostol acid—Approximately 20 minutes {01}.

Peak serum concentration:

Diclofenac—1.5 and 2 mcg/mL (50- and 75-mg doses, respectively) {01}.

Misoprostol acid—441 and 304 pg/mL (50– and 75–mg doses, respectively){02}

Duration of action:

Misoprostol—Approximately 3 hours {01}.

Elimination:


Diclofenac—


Renal—
        Approximately 65% (little or none unchanged) {01}.



Biliary—
        Approximately 35% (little or none unchanged) {01}.




Misoprostol—


Renal—
         70% {01}.




Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to diclofenac or other nonsteroidal anti-inflammatory drugs (NSAIDs), misoprostol or other prostaglandins, or prostaglandin analogs may be sensitive to diclofenac and misoprostol combination {01}.

Diclofenac and misoprostol combination may cause bronchoconstriction or anaphylaxis in aspirin-sensitive asthmatics, especially those with aspirin-induced nasal polyps, asthma, and other allergic reactions (the “aspirin triad”){01}.

Carcinogenicity/Tumorigenicity

Diclofenac—No evidence of tumorigenicity was found in rats receiving oral doses of diclofenac of up to 2 mg per kilogram of body weight (mg/kg) per day (approximately 12 mg per square meter of body surface area [mg/m 2] per day) for 24 months {01}. Studies in male and female mice receiving doses of diclofenac of up to 0.3 mg/kg per day (approximately 0.006 times the maximum recommended human dose [MRHD] on a mg/m 2 basis) and 1 mg/kg per day (approximately 0.02 times the MRHD on a mg/m 2 basis) for 24 months, respectively, showed no carcinogenic potential {01}.

Misoprostol—No evidence of carcinogenicity was found in rats and mice receiving oral doses of misoprostol of up to 2.4 mg/kg per day (approximately 24 times the MRHD on a mg/m 2 basis) for 24 months and doses of up to 16 mg/kg per day (approximately 80 times the MRHD on a mg/m 2 basis) for 21 months, respectively {01}.

Mutagenicity

Diclofenac and misoprostol combination was not genotoxic in the Ames test, Chinese hamster ovary cell (CHO/HGPRT) forward mutation test, rat lymphocyte chromosome aberration test, or in a mouse micronucleus test {01}.

Pregnancy/Reproduction
Fertility—
Diclofenac: Studies in male and female rats receiving doses of diclofenac of up to 4 mg/kg per day (approximately 0.16 times the MRHD on a mg/m 2 basis) found no effect on fertility and reproductive performance {01}.

Misoprostol: Fertility studies done in male and female rats receiving oral doses from 0.1 to 10 mg/kg per day (approximately 1 to 100 times the MRHD on a mg/m 2 basis) found dose-related preimplantation and postimplantation losses {01}. In addition, a significant decrease in the number of live pups born was observed at the highest dose {01}. These results suggest that misoprostol may have adverse effects on fertility {01}.

Pregnancy—
Diclofenac and misoprostol combination is contraindicated in pregnancy {01}.

Diclofenac and misoprostol combination was not teratogenic in reproductive studies in rabbits receiving oral doses of up to 10 mg/kg per day (approximately 0.8 times the MRHD on a mg/m 2 basis) of diclofenac and 0.04 mg/kg per day (approximately 0.8 times the MRHD on a mg/m 2 basis) of misoprostol {01}.

FDA Pregnancy Category X {01}.

Patients of childbearing potential may use diclofenac and misoprostol combination if nonsteroidal anti-inflammatory drug (NSAID) therapy is required and patient is at high risk of complications from gastric ulcers associated with the use of NSAIDs, or is at high risk of developing gastric ulceration {01}. Such patients must comply with effective contraceptive measures, must have had a negative serum pregnancy test within 2 weeks prior to initiation of therapy, and must start diclofenac and misoprostol combination only on the second or third day of the next normal menstrual period {01}. Additionally, patients must receive both oral and written warnings of the hazards of misoprostol, such as the risk of possible contraception failure and the danger to other women of childbearing potential should the drug be taken by mistake {01}.

Diclofenac: Diclofenac may cause premature closure of the ductus arteriosus, which may affect the fetal cardiovascular system {01}. Also, diclofenac, like other NSAIDs, may inhibit uterine contractions {01}.

No teratogenicity was demonstrated in reproductive studies in rabbits receiving oral doses of diclofenac of up to 10 mg/kg per day (approximately 0.8 times the MRHD on a mg/m 2 basis) per day, in mice receiving oral doses of up to 20 mg/kg per day (approximately 0.4 times the MRHD on a mg/m 2 basis), or in rats receiving oral doses of up to 10 mg/kg per day (approximately 0.4 times the MRHD on a mg/m 2 basis) {01}.

Misoprostol: Studies in humans have shown that misoprostol causes an increase in the frequency and intensity of uterine contractions {01}. Misoprostol administration has also been associated with a higher incidence of uterine bleeding and expulsion of uterine contents {01}. Miscarriages caused by misoprostol may be incomplete {01}.

No teratogenicity was demonstrated in reproductive studies in rats receiving oral doses of misoprostol of up to 1.6 mg/kg per day (approximately 16 times the MRHD on a mg/m 2 basis) or in rabbits receiving oral doses of up to 1 mg/kg per day (approximately 20 times the MRHD on a mg/m 2 basis) {01}.

Breast-feeding

Diclofenac and misoprostol combination is not recommended for use in nursing mothers {01}.

Diclofenac—Diclofenac is distributed into breast milk {01}.

Misoprostol—It is not known whether misoprostol is distributed into breast milk {01}. Since misoprostol is rapidly metabolized, it is unlikely to be distributed into breast milk {01}. Although studies have not been done, it is possible that the active metabolite (misoprostol acid) may be distributed into breast milk {01}.

Pediatrics

Appropriate studies on the relationship of age to the effects of diclofenac and misoprostol combination have not been performed in children up to 18 years of age {01}. Safety and efficacy have not been established.


Geriatrics


Studies in approximately 500 patients 65 years of age or older have not demonstrated geriatrics-specific problems that would limit the use of diclofenac and misoprostol combination in the elderly {01}. However, nonsteroidal anti-inflammatory drug (NSAID)–induced adverse effects may be less tolerable in geriatric patients than in younger patients {01}. Also, elderly patients are more likely to have age-related renal function impairment, which may require close monitoring in patients receiving diclofenac and misoprostol combination {01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antacids, especially magnesium-containing    (concurrent use of diclofenac may delay the absorption of diclofenac {01})

    (concurrent use with misoprostol may aggravate misoprostol-induced diarrhea {01})


» Anticoagulants, coumarin- or indandione-derivative or
» Corticosteroids, glucocorticoid    (concurrent use of diclofenac may result in increased risk of gastrointestinal bleeding {01})


Antidiabetic agents, oral or
Insulin    (diclofenac may cause changes in the effects of insulin or oral hypoglycemic agents; dosage adjustment of the antidiabetic agent may be necessary {01})


Antihypertensives, such as:
Angiotensin-converting enzyme (ACE) inhibitors
Diuretics, especially
» Potassium-sparing diuretics    (increased monitoring of the response to antihypertensive agents is advisable when diclofenac is used concurrently because diclofenac has been shown to inhibit the effects of antihypertensives; caution is recommended {01})

    (concurrent use of potassium-sparing diuretics with diclofenac may increase the risk of hyperkalemia {01})

    (concurrent use of diuretics and ACE inhibitors with diclofenac may increase the risk of renal failure secondary to the decrease in renal blood flow caused by inhibition of renal prostaglandin synthesis)

{01}
» Aspirin    (concurrent use with diclofenac is not recommended; use with aspirin may result in a lower plasma concentration, peak plasma levels, and area under the plasma concentration–time curve of diclofenac {01})


» Cyclosporine    (inhibition of renal prostaglandin activity by diclofenac may increase the plasma concentration of cyclosporine and/or the risk of cyclosporine-induced nephrotoxicity; patients should be monitored carefully during concurrent use {01})


» Digitalis glycosides    (diclofenac has been shown to increase serum digoxin concentrations leading to an increased risk of digitalis toxicity; increased monitoring for digitalis toxicity is recommended during concurrent use with diclofenac and misoprostol combination {01})


» Lithium    (inhibition of renal prostaglandin activity by diclofenac may result in an increase in the plasma concentration of lithium and a decrease in its renal clearance; patients should be monitored carefully for signs of lithium toxicity {01})


» Methotrexate    (diclofenac may decrease protein binding and/or renal elimination of methotrexate, resulting in increased and prolonged methotrexate plasma concentrations and an increased risk of toxicity; close monitoring is recommended, especially in patients with renal function impairment {01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]), serum or
Aspartate aminotransferase (AST [SGOT]), serum    (values may be increased; liver function test abnormalities may return to normal after discontinuation of therapy {01}; however, if significant abnormalities occur, clinical signs and symptoms consistent with liver disease develop, or systemic manifestations such as eosinophilia or rash occur, the medication should be discontinued {01})

    (in clinical trials with diclofenac, elevations of AST of more than 3 times the upper limit of normal occurred with overall rates of 2% in patients treated for 2 months and of ALT and/or AST in 4% of patients treated for 2 to 6 months {01}; values in excess of 8 times the upper limit of normal occurred in approximately 1% of the patients {01})


Platelet aggregation    (may be decreased with diclofenac {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Allergic reaction, severe, such as anaphylaxis or angioedema, induced by aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs), history of or {01}
» Nasal polyps associated with bronchospasm, aspirin-induced     (high risk of severe allergic reaction because of cross-sensitivity {01})


» Renal disease, severe    (use is not recommended {01})


» Sensitivity to diclofenac or other NSAIDs, misoprostol, or other prostaglandins {01}
Risk-benefit should be considered when the following medical problems exist
Anemia or
Asthma    (may be exacerbated {01})


Bleeding problems, including:
» Coagulation disorders
» Platelet disorders    (increased risk of bleeding due to the inhibition of platelet aggregation; diclofenac and misoprostol combination does not generally affect platelet counts, prothrombin time, or partial thromboplastin time; careful monitoring is recommended {01})


Conditions predisposing to and/or exacerbated by fluid retention, such as:
Compromised cardiac function
Congestive heart disease
Edema, preexisting
Hypertension
Renal function impairment or failure    (diclofenac and misoprostol combination may cause fluid retention and edema {01})


Conditions predisposing to gastrointestinal toxicity, such as:
Alcoholism, active
» Gastrointestinal bleeding, history of
Helicobacter pylori–positive status
» Peptic ulcer disease, history of
Tobacco use, or recent history of    (diclofenac and misoprostol combination should be used with extreme caution in patients with peptic ulcer disease or gastrointestinal bleeding {01}; dosage adjustment is recommended to minimize potential risk of gastrointestinal bleeding {01})


Congestive heart failure or
Extracellular volume depletion or
» Hepatic function impairment or
» Renal function impairment    (increased risk of renal failure secondary to the decrease in renal blood flow caused by inhibition of renal prostaglandin synthesis {01})

    (diclofenac and its metabolites are excreted primarily via the kidney {01}; therefore, the risk of toxicity associated with the accumulation of diclofenac may be increased; close monitoring is recommended {01})


Dehydration    (rehydration recommended before initiation of treatment with diclofenac and misoprostol combination)


Porphyria, hepatic    (diclofenac may precipitate an acute attack {01})


Systemic lupus erythematosus    (patient may be predisposed to aseptic meningitis {01})


» Caution is also recommended in geriatric patients, who may be more likely to develop adverse hepatic or renal effects with diclofenac and in whom gastrointestinal ulceration or bleeding is more likely to cause serious consequences {01}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood counts, complete (CBC) and
Chemistry profile, blood    (routine monitoring is recommended {01})


Hemoglobin determinations and/or
Hematocrit determinations    (although routine monitoring is not necessary for most patients during therapy, appropriate tests should be performed if symptoms of anemia occur {01})


Liver function tests, especially determination of transaminase (AST [SGOT]; ALT [SGPT]) serum values    (it is recommended that hepatic function tests be performed within 4 to 8 weeks following initiation of diclofenac and misoprostol combination therapy and periodically thereafter {01})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Cardiovascular effects, including arrhythmias {01} (irregular heartbeat), hypertension {01} (increased blood pressure ), hypotension {01} ( lightheadedness or dizziness), palpitations {01} (pounding heartbeat), syncope {01} ( fainting), and tachycardia {01} (increased heart rate)
    
central nervous system effects, including confusion {01}
hallucinations {01} (seeing, hearing, or feeling things that are not there), meningitis, aseptic {01} (severe headache; drowsiness; confusion; stiff neck and/or back; general feeling of illness or nausea)
    
fluid retention
    
gastrointestinal bleeding {01}
    
gastrointestinal ulceration, including {01}
esophageal {01}
gastric {01}
or peptic ulceration {01} (severe stomach pain, cramping, or burning; bloody, or black tarry stools; vomiting of material that looks like coffee grounds; severe and continuing nausea; heartburn and/or indigestion)
    
hematologic effects, including agranulocytosis {01} (fever with or without chills ; sores, ulcers, or white spots on lips or in mouth; sore throat), aplastic anemia {01} (shortness of breath, troubled breathing, tightness in chest, and/or wheezing; sores, ulcers, or white spots on lips or in mouth; sore throat), ecchymosis {01} (large, flat blue or purplish patches in the skin), hemolytic anemia {01} ( troubled breathing, exertional; unusual tiredness or weakness), leukopenia {01} (rarely, fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination ), purpura (bruises and/or red spots on skin), thrombocytopenia {01} (rarely, unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)— usually asymptomatic
    
hepatitis or jaundice {01} ( chills; fever; itching of the skin; nausea; yellow eyes or skin; stomach pain; unusual tiredness)
    
intestinal perforation {01} (severe pain, cramping, or burning; bloody, or black tarry stools ; vomiting of material that looks like coffee grounds; severe and continuing nausea; heartburn and/or indigestion )
    
mood or mental changes, including disorientation {01}
mental depression {01}
psychotic reaction {01}
    
pancreatitis {01} ( fever with or without chills; stomach pain; swelling and/or tenderness in upper stomach)
    
rectal bleeding {01}
    
renal failure {01} (increased blood pressure ; shortness of breath, troubled breathing, tightness in chest and/or wheezing; sudden decrease in the amount of urine; swelling of face, fingers, feet, and/or lower legs; continuing thirst; unusual tiredness or weakness; weight gain)
    
seizures {01}
    
Steven-Johnson syndrome {01} ( bleeding or crusting sores on lips; chest pain; fever with or without chills ; muscle cramps or pain; skin rash; sores, ulcers, or white spots on mouth; sore throat)

Note: A 6-week study in 572 patients with osteoarthritis receiving diclofenac and misoprostol combination (50 mg of diclofenac and 200 mcg of misoprostol three times daily or 75 mg of diclofenac and 200 mcg of misoprostol twice daily) found a statistically significant lower incidence of gastric ulcers compared to patients receiving diclofenac 75 mg twice daily {01}.


Rare
    
Anaphylaxis or anaphylactoid reactions {01} (changes in facial skin color; skin rash, hives, and/or itching; fast or irregular breathing; puffiness or swelling of the eyelids or around the eyes; shortness of breath, troubled breathing, tightness in chest, and/or wheezing )
    
severe hepatic reactions {01} (chills; fever; itching of the skin; nausea; yellow eyes or skin; stomach pain; unusual tiredness)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal pain {01}
    
diarrhea {01}
    
dyspepsia {01} (heartburn)
    
flatulence {01} (gas)
    
nausea{01}

Note: Diarrhea is dose-related, usually developing early in the course of therapy, and self-limiting, often resolving in 2 to 7 days {01}.


Incidence less frequent
    
Abnormal vision {01}
    
acne {01}
    
alopecia {01} (loss of hair)
    
anorexia {01} (decreased appetite )
    
central nervous system effects, including drowsiness {01}
irritability or nervousness {01}
    
dry mouth {01}
    
dysphagia {01} (trouble in swallowing)
    
impotence {01} (decrease in sexual ability)
    
migraine {01} (headache, severe and throbbing; sometimes with nausea or vomiting)
    
myalgia {01} (muscle pain)
    
paresthesias {01} (tingling, burning, or prickling sensations)
    
taste perversion {01} (change in sense of taste)
    
tremor {01} (trembling or shaking)
    
vaginal bleeding {01}





Overdose
For specific information on the agents used in the management of diclofenac and misoprostol combination overdose, see the Charcoal, Activated (Oral-Local) monograph.

For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and/or chronic
    
Bradycardia (slow heartbeat)
    
confusion {01}
    
drowsiness {01}
    
dyspnea {01} (shortness of breath)
    
fever {01}
    
gastrointestinal effects {01} (diarrhea; nausea and/or vomiting; stomach pain )
    
hypotension (decrease in blood pressure)
    
palpitations {01} (pounding heartbeat)
    
tremor {01} ( trembling or shaking)
    
seizures {01}


Treatment of overdose


To decrease absorption:
Emptying the stomach via gastric lavage; administering activated charcoal{01}



To enhance elimination:
Inducing diuresis{01}



Supportive care:
Monitoring and supporting vital functions.{01}

Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Diclofenac and Misoprostol (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to diclofenac or misoprostol

Allergies to aspirin or any other nonsteroidal anti-inflammatory drugs (NSAIDs), or other prostaglandins or prostaglandin analogs

Pregnancy—Use of diclofenac and misoprostol combination is contraindicated during pregnancy; patients of childbearing potential must take measures to assure they are not pregnant prior to therapy and to prevent pregnancy during therapy





Breast-feeding—Diclofenac is distributed into breast milk





Use in the elderly—Increased risk of toxicity
Other medications, especially anticoagulants, coumarin- or indandione-derivative, corticosteroids, aspirin, cyclosporine, digitalis glycosides, lithium, methotrexate, potassium-sparing diuretics
Other medical problems, especially allergic reaction (severe), aspirin-induced nasal polyps associated with bronchospasm, coagulation disorders, gastrointestinal bleeding or history of, hepatic function impairment, peptic ulcer disease or history of, platelet disorders, renal disease (severe) or history of, or renal function impairment

Proper use of this medication
» Not taking more medication than prescribed

Not taking with magnesium-containing antacids

Not chewing, crushing, or dissolving tablets

Not giving medication to another person

Taking with or after meals

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Stopping medication and checking with physician immediately if pregnancy is suspected

Consulting physician if diarrhea develops and continues for more than a week

Regular visits to physician during prolonged therapy

» Possibility of gastrointestinal ulceration or bleeding

» Possibility that alcohol may increase the risk of ulceration

Not taking NSAIDs, including ketorolac, concurrently, and not taking acetaminophen or aspirin or other salicylates for more than a few days while receiving diclofenac and misoprostol combination, unless concurrent use is prescribed by, and patient remains under the care of, a physician or dentist


Side/adverse effects
Signs of potential side effects, especially cardiovascular effects, central nervous system effects, fluid retention, gastrointestinal bleeding, gastrointestinal ulceration, hematologic effects, hepatic effects, intestinal perforation, mood or mental changes, pancreatitis, rectal bleeding, renal effects, seizures, Steven-Johnson syndrome, anaphylaxis or anaphylactoid reactions


General Dosing Information
Diclofenac and misoprostol combination should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. To minimize the risk for potential adverse events, the lowest effective dose should be used for the shortest possible duration {01}.

Diclofenac and misoprostol combination is not recommended for patients who would not receive the appropriate dose of both ingredients.


Oral Dosage Forms

DICLOFENAC AND MISOPROSTOL TABLETS

Usual adult dose
Osteoarthritis
Oral, 50 mg of diclofenac and 200 mcg of misoprostol three times a day {01}.

Rheumatoid arthritis
Oral, 50 mg of diclofenac and 200 mcg of misoprostol three to four times a day {01}.
Rheumatoid arthritis and osteoarthritis (for patients who experience intolerance)
Oral, 50 mg of diclofenac and 200 mcg of misoprostol two times a day or 75 mg of diclofenac and 200 mcg of misoprostol two times a day {01}.


Note: Dosage may also be individualized using separate products of diclofenac and misoprostol {01}. Thereafter, the patient may be changed to the appropriate diclofenac and misoprostol combination dose {01}. If clinically indicated, misoprostol may be used with diclofenac and misoprostol combination to optimize the misoprostol drug regimen {01}.



Usual adult prescribing limits
In osteoarthritis—150 mg of diclofenac and 800 mcg of misoprostol {01}.
In rheumatoid arthritis—225 mg of diclofenac and 800 mcg of misoprostol {01}.

Usual pediatric dose
Safety and efficacy have not been established in persons younger than 18 years of age {01}.

Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


50 mg of diclofenac and 200 micrograms of misoprostol (Rx) [Arthrotec 50{01} (colloidal silicon dioxide) (corn starch ) (crospovidone) (hydrogenated castor oil) (hydroxypropyl methylcellulose) (lactose) (magnesium stearate) (methacrylic acid copolymer) (micro-crystalline cellulose) (povidone (polyvidone) K-30) (sodium hydroxide) (talc) (triethyl citrate)]


75 mg of diclofenac and 200 micrograms of misoprostol (Rx) [Arthrotec 75{01} (colloidal silicon dioxide) (corn starch ) (crospovidone) (hydrogenated castor oil) (hydroxypropyl methylcellulose) (lactose) (magnesium stearate) (methacrylic acid copolymer) (micro-crystalline cellulose) (povidone (polyvidone) K-30) (sodium hydroxide) (talc) (triethyl citrate)]

Canada—


50 mg of diclofenac and 200 micrograms of misoprostol (Rx) [Arthrotec 50{02} (castor oil) (cellulose) (cellulose acetate phthalate) (colloidal silicon dioxide) (corn starch) ( crospovidone) (diethyl phthalate) (hydroxypropyl methylcellulose) (lactose ) (magnesium stearate) ( methacrylic acid copolymer) (povidone) (talc)]


75 mg of diclofenac and 200 micrograms of misoprostol (Rx) [Arthrotec 75{02} (castor oil) (cellulose) (colloidal silicon dioxide) (corn starch ) (crospovidone) (hydrogenated castor oil) (hydroxypropyl methylcellulose) (lactose) (magnesium stearate) (methacrylic acid copolymer) (povidone ) (sodium hydroxide) ( talc) (triethyl citrate)]

Packaging and storage:
Store at or below 25 ºC (77 ºF){01}.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • Take with food.
   • Do not take this medication if you are pregnant.



Developed: 05/27/1998
Revised: 04/20/2000



References
  1. Product Information: Arthrotec®, diclofenac sodium and misoprostol. Searle, Skokie, IL (PI revised 1/2000) reviewed 4/2000.
  1. Product Information: Arthrotec®, diclofenac sodium and misoprostol. Searle,Canada. In: Welbanks L (ed): Compendium of Pharmaceuticals and Specialties, 35th ed. Canadian Pharmaceutical Association, Ottawa, Ontario, Canada, 2000: p. 136–139.
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