Diclofenac Sodium / MisoprostolPronunciation
Pronunciation: dye-KLOE-fen-ak SOE-dee-um MYE-soe-PROST-ol
Class: Nonnarcotic analgesic combination
- Tablets, oral diclofenac sodium 50 mg/misoprostol 200 mcg
- Tablets, oral diclofenac sodium 75 mg/misoprostol 200 mcg
Diclofenac, an NSAID, decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis. Misoprostol, a prostaglandin E 1 analogue, provides gastric antisecretory and mucosal protective properties.
Indications and Usage
Treatment of signs and symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA) in patients at high risk of developing NSAID-induced gastric and duodenal ulcers and their complications.
Pregnancy; sensitivity to aspirin or any NSAID; sensitivity to misoprostol or other prostaglandins; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
Dosage and AdministrationOA
PO 50 mg/200 mcg three times daily. For patients experiencing intolerance, 50 mg/200 mcg or 75 mg/200 mcg twice daily can be used, but is less effective at preventing ulcers. Dosages of diclofenac higher than 150 mg/day and misoprostol 800 mcg/day in osteoarthritis are not recommended.RA
PO 50 mg/200 mcg three or four times daily. For patients experiencing intolerance, 50 mg/200 mcg or 75 mg/200 mcg twice daily can be used, but is less effective at preventing ulcers. Dosages of diclofenac higher than 225 mg/day and misoprostol 800 mcg/day in RA are not recommended.
- Administer tablet whole; do not crush, chew, or dissolve.
- Administer the lowest effective dose for the shortest duration consistent with treatment goals.
- May administer with meals.
- No more than 200 mcg of misoprostol should be administered at one time.
Store tablets at or below 77°F. Protect from moisture.
Drug InteractionsACE inhibitors
Antihypertensive effect may be decreased by diclofenac. In addition, the risk of nephrotoxicity may be increased. Closely monitor BP. If BP control deteriorates, consider stopping diclofenac/misoprostol. Periodic measurement of renal function and potassium concentrations is warranted.Alcohol, corticosteroids, smoking
The risk of GI bleeding may be increased. Monitor for signs of GI bleeding.Aminoglycosides (eg, amikacin, gentamicin, tobramycin)
Aminoglycoside plasma concentrations may be elevated in premature infants because diclofenac may reduce the glomerular filtration rate. If this combination cannot be avoided, reduce the aminoglycoside dose prior to starting diclofenac/misoprostol or stop diclofenac/misoprostol before starting aminoglycoside therapy. Monitor aminoglycoside concentrations and renal function.Antacids
Bioavailability of misoprostol may be reduced and absorption of diclofenac may be delayed. Magnesium-containing antacids increase risk of misoprostol-associated diarrhea.Aspirin
Risk of serious GI complications, including bleeding, may be increased. In addition, the cardioprotective effect of aspirin may be reduced. Concurrent use of diclofenac and aspirin is not generally recommended.Azole antifungals (eg, fluconazole, voriconazole)
Diclofenac plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor the clinical response and adjust the dose of diclofenac/misoprostol as needed.Bile acid sequestrants (eg, cholestyramine, colestipol)
The effects of diclofenac may be decreased. If an interaction is suspected, consider increasing the diclofenac/misoprostol dose during administration of cholestyramine.Bisphosphonates (eg, alendronate)
Risk of gastric ulceration may be increased. Use with caution. Monitor for signs of GI adverse reactions, especially gastric ulceration.Cyclosporine
Risk of cyclosporine toxicity, including nephrotoxicity, may be increased. Closely monitor renal function and cyclosporine concentrations. If an interaction is suspected, consider decreasing the cyclosporine dosage or stopping diclofenac/misoprostol.Digoxin
Diclofenac may elevate digoxin levels, increasing risk of toxicity. Monitor for possible digoxin toxicity.Diuretics (eg, loop diuretics [eg, furosemide], potassium-sparing diuretics [eg, triamterene], thiazide diuretics [eg, chlorothiazide])
The natriuretic effect of furosemide and thiazide diuretics may be reduced. Coadministration of potassium-sparing diuretics may increase serum potassium levels.Heparins (eg, dalteparin, enoxaparin, heparin)
The risk of hemorrhagic adverse reactions may be increased. If concurrent use cannot be avoided, close clinical and laboratory monitoring are warranted.Hypoglycemic agents, oral
Both hypo- and hyperglycemia may occur, necessitating a change in the hypoglycemic agent dosage. Monitor blood glucose and adjust the oral hypoglycemic dose as needed.Lithium
Lithium levels may be elevated, increasing risk of toxicity. Monitor for signs of lithium toxicity. Additional lithium plasma concentration monitoring is warranted. Adjust the lithium dose as needed.Methotrexate
May increase methotrexate levels and risk of toxicity. If coadministration cannot be avoided, use with caution. Monitor for signs of methotrexate toxicity. Monitoring methotrexate concentrations may be useful in managing treatment.Phenobarbital
Phenobarbital toxicity has been reported following the initiation of diclofenac therapy. Monitor for phenobarbital toxicity.Probenecid
Diclofenac plasma concentrations may be elevated, increasing the risk of toxicity. Monitor for signs of diclofenac toxicity and adjust treatment as needed.Quinolones (eg, norfloxacin)
Quinolone plasma concentrations may be elevated. The risk of CNS stimulation and seizures from quinolones may be increased. Use with caution.Serotonin reuptake inhibitors (eg, fluoxetine, venlafaxine)
The risk of upper GI bleeding may be increased. If coadministration cannot be avoided, close clinical monitoring for signs of GI bleeding is warranted. Consider shortening diclofenac/misoprostol treatment duration, decreasing the diclofenac/misoprostol dose, or using alternative therapy (eg, acetaminophen, tricyclic antidepressants).Sucralfate
The effects of diclofenac may be decreased, possibly because of decreased absorption. Monitor the clinical response and adjust treatment as needed.Warfarin
May increase risk of gastric erosion and bleeding. Closely monitor coagulation status and adjust the anticoagulant dose as needed. Monitor for signs of GI bleeding.
Arrhythmia, atrial fibrillation, CHF, hypertension, hypotension, MI, palpitations, phlebitis, premature ventricular contractions, syncope, tachycardia, vasculitis.
Coma, convulsions, depression, hallucinations, meningitis, psychotic reaction.
Erythema multiforme, exfoliative dermatitis, pemphigoid reaction, photosensitivity, skin ulceration, Stevens-Johnson syndrome, TEN.
Esophageal ulceration, GI bleeding, GI neoplasm benign, hematemesis, intestinal perforation, peptic ulcer, rectal bleeding.
Hematuria, interstitial nephritis, nephrotic syndrome, papillary necrosis, proteinuria, renal failure, vaginal hemorrhage.
Agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, thrombocythemia, thrombocytopenia.
Abnormal hepatic function, hepatitis, jaundice, liver failure, pancreatitis.
Angioedema, laryngeal/pharyngeal edema, urticaria.
Pneumonia, pulmonary embolism, respiratory depression.
Death, infection, sepsis.
Misoprostol can cause abortion, premature birth, and birth defects in women who are pregnant. Uterine rupture has been reported when misoprostol was given to pregnant women to induce labor or abortion after the eighth week of pregnancy. Ensure that misoprostol is not being used by women of childbearing potential unless the patient requires NSAID therapy and is at high risk of developing gastric ulcers associated with NSAID use. Such patients must have a negative serum pregnancy test within 2 wk prior to beginning therapy; be capable of complying with effective contraceptive measures; receive both oral and written warnings of the hazards of misoprostol, risk of contraception failure, and danger to other women of childbearing potential if they take the medication by mistake; and begin drug only on second or third day of next normal menstrual period.CV risk
NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with length of therapy. Patients with CV disease or risk factors for CV disease may be at greater risk. Diclofenac/misoprostol is contraindicated for treatment of perioperative pain in the setting of CABG surgery.GI risk
NSAIDs cause an increased risk of serious GI adverse reactions, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These reactions can occur at any time during use, with or without warning symptoms. Elderly patients are at greater risk of serious GI events.
Monitor Hgb and Hct in patients on long-term therapy exhibiting signs or symptoms of anemia. Monitor liver enzymes within 4 to 8 wk after starting therapy then periodically thereafter. Monitor for signs and symptoms of GI bleeding. Check BP, CBC, and chemistry profile periodically in patients receiving long-term treatment. Monitor renal function in elderly patients. Monitor for fluid retention and edema in patients taking NSAIDs.
Category X .
Not recommended in breast-feeding mothers.Diclofenac
Excreted in breast milk.Misoprostol
The active metabolite, misoprostol acid, is excreted in breast milk.
Safety and efficacy have not been established.
Increased risk of adverse reactions. Select dose with caution because elderly patients are more likely to have decreased renal function.
NSAIDs may cause a further decrease in renal function in patients with preexisting renal function impairment. Use is not recommended in patients with advanced renal disease.
Diclofenac can cause abnormal LFTs, often within the first 2 mo of therapy.
May occur in patients without known prior exposure to diclofenac. Do not administer this product to patients with the aspirin triad. Severe, potentially fatal bronchospasm may occur.
Has been reported and may be caused by fluid retention, occult or gross GI blood loss, or an incompletely described effect on erythropoiesis.
Aseptic meningitis with fever and coma may occur and may be more likely in patients with systemic lupus and related connective tissue diseases.
Patients with asthma may have aspirin-sensitive asthma, which may be associated with severe and sometimes fatal bronchospasm. Do not administer diclofenac/misoprostol to patients with this type of aspirin sensitivity because of possible cross-reactivity.
Fluid retention and edema may occur; use with caution in patients with fluid retention or heart failure.
NSAIDs interfere with platelet function and vascular response to bleeding; use with caution in patients with coagulation disorders or those who are receiving anticoagulants.
Onset of new hypertension or worsening of preexisting hypertension may occur, increasing the risk of CV reactions.
Avoid use in patients with hepatic porphyria.
Long-term administration of diclofenac may cause renal injury, including renal papillary necrosis. Renal toxicity may occur in patients in whom renal prostaglandins have a compensatory role in maintaining renal perfusion.
Serious and sometimes fatal skin adverse reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and TEN, may occur.
Aspiration pneumonitis, confusion, death, drowsiness, general hypotonia, GI complaints, increased intracranial pressure, loss of consciousness, vomiting.Misoprostol
Abdominal pain, bradycardia, convulsions, diarrhea, dyspnea, fever, GI discomfort, hypotension, palpitations, sedation, tremor.
- Advise patient to read the patient information leaflet before using product the first time and with each refill.
- Advise patients of the abortifacient property and not to share this drug with others.
- Caution women not to take this medicine if pregnant and to take measures to prevent pregnancy, including using effective contraception, while on this drug. If a patient suspects she is pregnant, advise her to stop taking the drug and to contact health care provider immediately.
- Advise women who become pregnant or intend to become pregnant during therapy to notify health care provider.
- Advise women to avoid pregnancy for at least 1 month or through 1 menstrual cycle after stopping the medication.
- Instruct patient to report any signs or symptoms of GI ulceration or bleeding, skin rash, swelling, or weight gain to health care provider.
- Instruct patient not to take drug and to seek immediate medical attention if signs of liver toxicity occur, including fatigue, flu-like symptoms, itching, jaundice, lethargy, nausea, or right upper quadrant tenderness.
- Caution breast-feeding mothers to discontinue breast-feeding because of potential harm to the baby.
- Instruct patient to seek immediate medical attention if difficulty breathing or swelling of the face or throat occurs.
- Tell patient that abdominal pain, diarrhea, nausea, and upset stomach may develop during first few weeks of therapy and usually stop after approximately 1 wk of continued treatment. To minimize diarrhea, advise patient to take with meals and to avoid antacids containing magnesium. If symptoms persist for more than 7 days or if symptoms become severe, instruct patient to notify health care provider.
- Instruct patients to swallow tablet whole, and not to crush, chew, or dissolve.
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