Dicloenac Sodium And Misoprostol
FDA Drug Information • Also known as: Dicloenac Sodium And Misoprostol Dr
- Brand Names
- Dicloenac Sodium And Misoprostol Dr
- Drug Class
- Prostaglandin E1 Analog [EPC]
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: RISK OF UTERINE RUPTURE, ABORTION, PREMATURE BIRTH, BIRTH DEFECTS; SERIOUS CARDIOVASCULAR EVENTS; AND SERIOUS GASTROINTESTINAL EVENTS Uterine Rupture, Abortion, Premature Birth, and Birth Defects Administration of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets, to pregnant women can cause uterine rupture, abortion, premature birth, or birth defects. Uterine rupture has occurred when misoprostol was administered in pregnant women to induce labor or an abortion [see Warnings and Precautions ( 5.1) and Use in Specific Populations ( 8.1)] . Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in pregnancy [see Contraindications ( 4)] and not recommended in women of childbearing potential. Patients must be advised of the abortifacient property and warned not to give the drug to others [see Warnings and Precautions ( 5.1)] . If diclofenac sodium and misoprostol delayed-release tablets are prescribed, verify the pregnancy status of females of reproductive potential prior to initiation of treatment and advise them to use effective contraception during treatment [see Use in Specific Populations ( 8.3)]. Cardiovascular Thrombotic Events NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions ( 5.2)] . Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications ( 4) and Warnings and Precautions ( 5.2)]. Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs cause an increased risk of serious gastrointestinal (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 [see Warnings and Precautions ( 5.3)] .
Description
11. Description Diclofenac sodium and misoprostol delayed-release tablets, USP is a combination product containing diclofenac sodium, an NSAID with analgesic properties, and misoprostol, a gastrointestinal (GI) mucosal protective prostaglandin-1 (PGE1) analog. Diclofenac sodium and misoprostol delayed-release tablets are white to off-white, round, biconvex, and approximately 11 mm in diameter. Each tablet consists of an enteric-coated core containing 50 mg (diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg) or 75 mg (diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg) of diclofenac sodium (equivalent to 46.39 mg or 69.58 mg of diclofenac, respectively) surrounded by an outer mantle containing 200 mcg misoprostol. Diclofenac sodium is a phenylacetic acid derivative that is a white to off-white, virtually odorless, crystalline powder. Diclofenac sodium is freely soluble in methanol, soluble in ethanol, and practically insoluble in chloroform and in dilute acid. Diclofenac sodium is sparingly soluble in water. Its chemical formula and name are: C 14H 10Cl 2NO 2Na [M.W. = 318.14] 2-[(2,6-dichlorophenyl) amino] benzeneacetic acid, monosodium salt. Misoprostol is a water-soluble, viscous liquid that contains approximately equal amounts of two diastereomers. Its chemical formula and name are: C 22H 38O 5 [M.W. = 382.54] (±) methyl 11α,16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate. Inactive ingredients in diclofenac sodium and misoprostol delayed-release tablets include: colloidal silicon dioxide; corn starch; crospovidone; hydrogenated castor oil; hypromellose; lactose monohydrate; magnesium stearate; methacrylic acid copolymer; microcrystalline cellulose; povidone; sodium hydroxide; talc; triethyl citrate.
What Is Dicloenac Sodium And Misoprostol Used For?
1. Indications and Usage Diclofenac sodium and misoprostol delayed-release tablets are indicated for treatment of the signs and symptoms of osteoarthritis or rheumatoid arthritis in adult patients at high risk of developing NSAID-induced gastric and duodenal ulcers and their complications. For a list of factors that may increase the risk of NSAID-induced gastric and duodenal ulcers and their complications [see Warnings and Precautions ( 5.3)] .
Dosage and Administration
2. Dosage and Administration 2.1 Important Dosage Information Carefully consider the potential benefits and risks of diclofenac sodium and misoprostol delayed-release tablets and other treatment options before deciding to use diclofenac sodium and misoprostol delayed-release tablets. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions ( 5)] . After observing the response to initial therapy with diclofenac sodium and misoprostol delayed-release tablets, the dose and frequency should be adjusted to suit an individual patient’s needs. Diclofenac sodium and misoprostol delayed-release tablets are not recommended for patients who would not receive the appropriate dosage of both active ingredients. Diclofenac sodium and misoprostol delayed-release tablets, a fixed combination product, is administered as diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg (50 mg diclofenac sodium and 200 mcg misoprostol) or diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg (75 mg diclofenac sodium and 200 mcg misoprostol). 2.2 Recommended Dosage in Patients with Osteoarthritis The recommended dosage for the treatment of osteoarthritis for maximal GI mucosal protection is diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg three times a day. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg two times a day or diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg two times a day can be used, but these dosages are less effective in preventing ulcers. A daily dosage of diclofenac sodium greater than 150 mg/day is not recommended. Daily doses of the components delivered with these regimens are as follows: Osteoarthritis Regimen Diclofenac Sodium (mg/day) Misoprostol (mcg/day) Diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg three times a day two times a day* 150 100 600 400 Diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg two times a day* 150 400 *For patients who experience intolerance; these dosages are less effective in preventing ulcers 2.3 Recommended Dosage in Patients with Rheumatoid Arthritis The recommended dosage for the treatment of rheumatoid arthritis is diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg three or four times a day. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg two times a day or diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg two times a day can be used, but are less effective in preventing ulcers. A daily dosage of diclofenac sodium greater than 200 mg/day is not recommended. Daily doses of the components delivered with these regimens are as follows: Rheumatoid Arthritis Regimen Diclofenac Sodium (mg/day) Misoprostol (mcg/day) Diclofenac sodium and misoprostol...
Side Effects (Adverse Reactions)
6. Adverse Reactions The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions ( 5.2)] GI Bleeding, Ulceration and Perforation [see Warnings and Precautions ( 5.3)] Hepatotoxicity [see Warnings and Precautions ( 5.4)] Hypertension [see Warnings and Precautions ( 5.5)] Heart Failure and Edema [see Warnings and Precautions ( 5.6)] Renal Toxicity and Hyperkalemia [see Warnings and Precautions ( 5.7)] Anaphylactic Reactions [see Warnings and Precautions ( 5.8)] Serious Skin Reactions [see Warnings and Precautions ( 5.10)] Hematologic Toxicity [see Warnings and Precautions ( 5.12)] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reaction information for diclofenac sodium and misoprostol delayed-release tablets is derived from multinational controlled clinical trials in over 2,000 patients receiving diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg or diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg, as well as from blinded, controlled trials of diclofenac sodium delayed-release tablets and misoprostol tablets. Gastrointestinal GI disorders had the highest reported incidence of adverse reactions for patients receiving diclofenac sodium and misoprostol delayed-release tablets. These events were generally minor, but led to discontinuation of therapy in 9% of patients on diclofenac sodium and misoprostol delayed-release tablets and 5% of patients on diclofenac sodium. For GI ulcer rates, [see Clinical Studies ( 14)]. GI disorder Diclofenac Sodium and Misoprostol Delayed-Release Tablets Diclofenac Sodium Abdominal pain 21% 15% Diarrhea 19% 11% Dyspepsia 14% 11% Nausea 11% 6% Flatulence 9% 4% Diclofenac sodium and misoprostol delayed-release tablets can cause more abdominal pain, diarrhea, and other GI symptoms than diclofenac alone. Diarrhea and abdominal pain developed early in the course of therapy, and were usually self-limited (resolved after 2 to 7 days). Rare instances of profound diarrhea leading to severe dehydration have been reported in patients receiving misoprostol. Patients with an underlying condition such as inflammatory bowel disease, or those in whom dehydration, were it to occur, would be dangerous, should be monitored carefully if diclofenac sodium and misoprostol delayed-release tablets are prescribed. The incidence of diarrhea can be minimized by administering diclofenac sodium and misoprostol delayed-release tablets with food and by avoiding co-administration with magnesium-containing antacids. Gynecological Gynecological disorders previously reported with misoprostol use have also been reported for women receiving diclofenac sodium and misoprostol delayed-release tablets (see below). Postmenopausal vaginal bleeding may be related to administration of diclofenac sodium and misoprostol delayed-release tablets. If it occurs, diagnostic workup should be undertaken to rule out gynecological pathology [see Boxed Warnings, Contraindications ( 4) and Warnings and Precautions ( 5)] . Other adverse experiences reported occasionally with diclofenac sodium and misoprostol delayed-release tablets, diclofenac or other NSAIDs, or misoprostol are: Body as a whole: asthenia, fatigue, malaise. Central and peripheral nervous system: dizziness, drowsiness, headache, insomnia, paresthesia, vertigo. Digestive: anorexia, appetite changes, constipation, dry mouth, dysphagia, esophageal ulceration, esophagitis, eructation, gastritis, gastroesophageal reflux, GI neoplasm benign, peptic ulcer, tenesmus, vomiting. Female reproductive disorders: breast pain, dysmenorrhea, menstrual disorder, menorrhagia, vaginal hemorrhage. Hemic and lymphatic...
Drug Interactions
7. Drug Interactions See Table 1 for clinically significant drug interactions with diclofenac and misoprostol. Table 1: Clinically Significant Drug Interactions with Diclofenac and Misoprostol Drugs That Interfere with Hemostasis Clinical Impact: Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of diclofenac sodium and misoprostol delayed-release tablets with anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding [see Warnings and Precautions ( 5.12)] . Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions ( 5.3)] . Intervention: Concomitant use of diclofenac sodium and misoprostol delayed-release tablets and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions ( 5.12)] . Diclofenac sodium and misoprostol delayed-release tablets are not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention: The concomitant administration of these drugs should be done with caution. Patients should be adequately hydrated and the clinical need to monitor the renal function should be assessed at the beginning of the concomitant treatment and periodically thereafter. During concomitant use of diclofenac sodium and misoprostol delayed-release tablets and ACE inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of diclofenac sodium and misoprostol delayed-release tablets and ACE inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal...
Contraindications
4. Contraindications Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in the following patients: Pregnancy. Use of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets, during pregnancy can result in maternal and fetal harm, including uterine rupture, abortion, premature birth, or birth defects [see Warnings and Precautions ( 5.1) and Use in Specific Populations ( 8.1)] In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions ( 5.2)] Active gastrointestinal bleeding [see Warnings and Precautions ( 5.3)] History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions ( 5.8, 5.9)] Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac sodium and misoprostol, other prostaglandins, or any components of the drug product [see Warnings and Precautions ( 5.8, 5.10)]
Overdosage
10. Overdosage Manage patients with symptomatic and supportive care following an acute NSAID overdosage. There are no specific antidotes. It is advisable to contact a poison control center (1-800-222-1222) to determine the latest recommendations because strategies for the management of overdose are continually evolving. The toxic dose of diclofenac sodium and misoprostol delayed-release tablets has not been determined. However, signs of overdosage from the components of the product have been described. Diclofenac Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions ( 5.2, 5.3, 5.5, 5.7)] . Clinical signs that may suggest diclofenac sodium overdose include GI complaints, confusion, drowsiness, or general hypotonia. If gastric decontamination may be potentially beneficial to the patient, e.g., short time since ingestion or a large overdosage (5 to 10 times the recommended dosage), consider emesis and/or activated charcoal (60 grams to 100 grams in adults, 1 gram to 2 grams per kg of body weight in pediatric patients) and/or an osmotic cathartic in symptomatic patients. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. Misoprostol The toxic dose of misoprostol in humans has not been determined. Cumulative total daily doses of 1600 mcg have been tolerated, with only symptoms of GI discomfort being reported. Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension, or bradycardia. Diclofenac Sodium and Misoprostol Delayed-Release Tablets Symptoms of acute overdosage with diclofenac sodium and misoprostol...
How Supplied
16. How Supplied/Storage and Handling Diclofenac sodium and misoprostol delayed-release tablets, USP are supplied as a uncoated tablets in dosage strengths of 75 mg diclofenac sodium/200 mcg misoprostol. 75 mg/200 mcg dosage strength is a white to off-white, round, biconvex uncoated tablet, debossed with “D 75 M” on one side and plain on other side. The dosage strengths are supplied in: Bottles of 60 Tablets NDC: 80425-0273-01 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.