Dosing & Uses
Dosage Forms & Strengths
diclofenac/misoprostol
tablet
- 50mg/200mcg
- 75mg/200mcg
Osteoarthritis
50 mg/200 mcg: 1 tab PO three times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day
75mg/200mcg: 1 tab PO three times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day
If not tolerated, may reduce frequency to twice daily
Three times daily dose of misoprostol is more protective than when given twice daily
Rheumatoid Arthritis
50 mg/200 mcg: 1 tab PO three or four times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day
75mg/200mcg: 1 tab PO three or four times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day
If not tolerated may reduce frequency to twice daily
Three times daily dose of misoprostol is more protective than when given twice daily
Administration
Swallow tablet whole, do not chew or crush
Do not take with antacids
Safety & efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Rash including erythematous, rash macular and maculo-papular (18%)
Pyrexia (15%)
Urticaria (13%)
Flushing (13%)
1-10%
Hypertension (10%)
Hyperhydrosis (8%)
Decreased oxygen saturation (8%)
Cough (8%)
Tachypnea (8%)
Tachycardia (8%)
Urticaria (8%)
Anaphylaxis (7%
Chest discomfort (7%)
Muscle twitching (7%)
Erythema (5%)
Vomiting (5%)
Rigors (5%)
Pallor (5%)
Cyanosis (5%)
Agitation (5%)
Tremor (5%)
Myalgia (5%)
Flushing (5%)
Peripheral edema (3%)
Pruritus (3%)
Rash, papular (3%)
Throat tightness (3%)
<1%
Fatigue
Malaise
Chills
Edema
Atrial fibrillation
Congestive heart failure
Myocardial infarction
Phlebitis
Vasculitis
Syncope
Dysphagia
Enteritis
Peptic ulcer
Vaginitis
Breast pain
Dysmenorrhea
Uterine cramping
Ulcerative stomatitis
Impotence
Perineal pain
Glycosuria
Alopecia
Postmarketing reports
Increased alanine aminotransferase
Increased alkaline phosphatase
Increased aspartate aminotransferase
Increased BUN
Dehydration
Glycosuria
Gout
Hypercholesterolemia
Hyperglycemia
Hyperuricemia
Hypoglycemia
Hyponatremia
Periorbital edema porphyria
Weight changes
Fluid retention
Warnings
Black Box Warnings
Cardiovascular Risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), & stroke, which can be fatal
- Risk may increase with duration of use
- Patients with risk factors for or existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke)
Gastrointestinal Risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, & perforation of the stomach or intestines, which can be fatal
- GI adverse events may occur at any time during use & without warning symptoms
- Elderly patients are at greater risk for serious GI events
Women with childbearing potential
- Advise patient or abortificient property and warn not to give to others; not for women of childbearing potential unless patient requires nonsteroidal anti-inflammatory drug (NSAID) therapy and is at high risk of developing gastric or duodenal ulceration or complications from gastric or duodenal ulcers associated with NSAID use
- Administration to women who are pregnant can cause abortion, premature birth, birth defects, or uttering rupture
- Uterine rupture reported when misoprostol was administered in pregnant women to induce labor or abortion
- Risk of uttering rupture increases with advancing gestational ages and with prior uttering surgery, including cesarean delivery; drug should not be administered to women who are pregnant
- Prescribe to patients of childbearing potential only if the following conditions are met:
- Has had a negative serum pregnancy test within 2 wk prior to beginning therapy
- Is capable of complying with effective contraceptive measures
- Has received both oral and written warnings of hazards of misoprostol, the risk of possible contraception failure, and danger to other women of childbearing potential should the drug be taken by mistake
- Will begin diclofenac only on second or third day of the next normal menstrual period
Contraindications
Hypersensitivity drugs or related products
Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; active gastrointestinal bleeding
Patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
Cautions
Women of childbearing potential (see mfr's package insert for restrictions)
Avoid pregnancy during & for at least 1 month after treatment
May cause blurred vision, drowsiness, dizziness
Transaminase elevation observed with chronic use
Hypokalemia may occur when administered with drugs capable of inducing hyperkalemia; risk may increase in diabetics, renal disease, the elderly
NSAIDs reported to cause serious skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome
May increase risk of aseptic meningitis especially in patients with mixed connective tissue disorders and systemic lupus erythematous
Severe bronchospasm may occur in patients with asthma
Use caution in hepatic impairment, porphyria (avoid if possible), hypertension, renal impairment
Avoid use of diclofenac/misoprostol with concomitant NSAIDs including COX inhibitors
Use lowest effective dose in patients with known cardiovascular (CV) disease or risk factors for CV
Concurrent use of aspirin with NSAIDs in mitigating CV thrombotic events not shown conclusively; increased risk of serious GI adverse reactions likely
Use caution in patients with hypertension; monitor blood pressure closely during initiation of NSAID treatment and throughout the course of therapy
Fluid retention and edema may occur with therapy; use with caution in patients with heart failure
Serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of stomach, small intestine, or large intestine, which can be fatal may occur
Renal papillary necrosis and other renal injury reported with NSAID long-term therapy
Toxic epidermal necrolysis, reported with NSAID use, especially within first month of therapy; discontinue use at first appearance of skin rash
Use of NSAIDs may diminish ability to diagnose conditions associated with pain or inflammation
Anemia reported with NSAID use; monitor
Use caution in patients with coagulation disorders or receiving anticoagulants; NSAIDs inhibit platelet aggregation
Not for administration to patients with aspirin-sensitive asthma; use caution in patients with preexisting asthma
NSAIDs may diminish antihypertensive effect of ACE-inhibitors
Not recommended in patients with advanced renal disease
Drug-induced hepatotoxicity reported in first month, and may occur within 1-6 months, but can occur at any time during therapy
Pregnancy & Lactation
Pregnancy
Contraindicated in pregnant women; administration of misoprostol to pregnant women can cause abortion, premature birth, birth defects or uterine rupture; congenital anomalies sometimes associated with fetal death reported subsequent to unsuccessful use of misoprostol as an abortifacient, but the drug’s teratogenic mechanism has not been demonstrated
Verify pregnancy status for females of reproductive potential within 2 weeks prior to initiating therapy
Drug can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment
Use of NSAIDS during third trimester of pregnancy increases risk of premature closure of fetal ductus arteriosus
Labor or delivery
- Some case reports and studies have associated misoprostol with risk of stillbirth, uterine hyperstimulation, perineal tear, amniotic fluid embolism, severe bleeding, shock, uterine rupture and death; the risk of uterine rupture associated with misoprostol use in pregnancy may occur at any gestational age, and increases with advancing gestational ages and with prior uterine surgery, including cesarean delivery; grand multiparity also appears to be a risk factor for uterine rupture
Infertility
- Based on mechanism of action, NSAIDs, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women
- Animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation; small studies in women have also shown a reversible delay in ovulation in women treated with NSAIDs; consider withdrawal of NSAIDs, in women who have difficulties conceiving or who are undergoing investigation of infertility
Animal data
- In reproduction studies with pregnant rabbits, there were no skeletal or visceral malformations when drug combination was administered during organogenesis at doses less than maximum recommended human doses (MRHD); however, embryotoxicity was observed at this exposure
- Based on animal data, prostaglandins have been shown to have important role in endometrial vascular permeability, blastocyst implantation, and decidualization; in animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre- and post-implantation loss; if a woman becomes pregnant while receiving therapy, discontinue drug and advise woman of potential risks to her and to a fetus
- In animal studies, NSAIDs are known to inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth
Lactation
No lactation studies conducted; however, limited published literature reports that diclofenac and active metabolite of misoprostol are present in breast milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Diclofenac: Inhibits cyclooxygenase-1 (COX-1) & -2 (COX-2), thereby inhibiting prostaglandin synthesis; has anti-inflammatory, antipyresis, and analgesic properties
Misoprostol: Replaces protective prostaglandins consumed by prostaglandin-inhibiting therapies (NSAID-induced ulcers)
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Formulary
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