Dosing and uses of Arthrotec (diclofenac/misoprostol)
Adult dosage forms and 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
Pediatric dosage forms and strengths
Safety & efficacy not established
Arthrotec (diclofenac/misoprostol) adverse (side) 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
- 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 and lactation
Pregnancy category: X
Lactation: Enters breast milk; use with caution
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 of Arthrotec (diclofenac/misoprostol)
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)
