ARTHROTEC- diclofenac sodium and misoprostol tablet, film coated
G.D. Searle LLC Division of Pfizer Inc.
WARNING: RISK OF UTERINE RUPTURE, ABORTION, PREMATURE BIRTH, BIRTH DEFECTS; AND SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
? ARTHROTEC? CONTAINS DICLOFENAC SODIUM AND MISOPROSTOL. ADMINISTRATION OF MISOPROSTOL TO WOMEN WHO ARE PREGNANT CAN CAUSE ABORTION, PREMATURE BIRTH, OR BIRTH DEFECTS. UTERINE RUPTURE HAS BEEN REPORTED WHEN MISOPROSTOL WAS ADMINISTERED IN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION BEYOND THE EIGHTH WEEK OF PREGNANCY. ARTHROTEC SHOULD NOT BE TAKEN BY PREGNANT WOMEN
? PATIENTS MUST BE ADVISED OF THE ABORTIFACIENT PROPERTY AND WARNED NOT TO GIVE THE DRUG TO OTHERS. ARTHROTEC should not be used in women of childbearing potential unless the patient requires nonsteroidal anti-inflammatory drug (NSAID) therapy and is at high risk of developing gastric or duodenal ulceration or for developing complications from gastric or duodenal ulcers associated with the use of the NSAID. In such patients, ARTHROTEC may be prescribed if the patient:
? has had negative serum pregnancy test within weeks prior to beginning therapy.
? is capable of complying with effective contraceptive measures.
? has received both oral and written warnings of the hazards of misoprostol, the risk of possible contraception failure, and the danger to other women of childbearing potential should the drug be taken by mistake.
? will begin ARTHROTEC only on the second or third day of the next normal menstrual period
? Cardiovascular Thrombotic Events
? Nonsteroidal anti-inflammatory drugs (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
? ARTHROTEC is contraindicated in the setting of coronary artery bypass graft (CABG) surgery
DESCRIPTION
ARTHROTEC (diclofenac sodium/misoprostol) is combination product containing diclofenac sodium, nonsteroidal anti-inflammatory drug (NSAID) with analgesic properties, and misoprostol, gastrointestinal (GI) mucosal protective prostaglandin E1 analog. ARTHROTEC oral 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 (ARTHROTEC 50) or 75 mg (ARTHROTEC 75) diclofenac sodium surrounded by an outer mantle containing 200 mcg misoprostol.
Diclofenac sodium is phenylacetic acid derivative that is 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:
C14 H10 Cl2 NO2 Na [M.W. 318.14] 2-[(2,6-dichlorophenyl) amino] benzeneacetic acid, monosodium salt.
Misoprostol is water-soluble, viscous liquid that contains approximately equal amounts of two diastereomers. Its chemical formula and name are:
C22 H38 O5 [M.W. 382.54] (?) methyl 11?,16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate.
Inactive ingredients in ARTHROTEC include: colloidal silicon dioxide; crospovidone; hydrogenated castor oil; hypromellose; lactose; magnesium stearate; methacrylic acid copolymer; microcrystalline cellulose; povidone (polyvidone) K-30; sodium hydroxide; starch (corn); talc; triethyl citrate.
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
ARTHROTEC (diclofenac/misoprostol) is combination product containing diclofenac, nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory and antipyretic properties, and misoprostol, GI mucosal protective prostaglandin E1 analog.
Diclofenac
The mechanism of action of diclofenac, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).
Diclofenac is potent inhibitor of prostaglandin (PG) synthesis in vitro. Diclofenac concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because diclofenac is an inhibitor of prostaglandin synthesis, its mode of action may be due to decrease of prostaglandins in peripheral tissues.
Misoprostol
Misoprostol is synthetic prostaglandin E1 analog with gastric antisecretory and mucosal protective properties. NSAIDs inhibit prostaglandin synthesis. deficiency of prostaglandins within the gastric and duodenal mucosa may lead to diminishing bicarbonate and mucus secretion and may contribute to the mucosal damage caused by NSAIDs.
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 prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events
INDICATIONS AND USAGE
? ARTHROTEC is indicated for treatment of the signs and symptoms of osteoarthritis or rheumatoid arthritis in patients at high risk of developing NSAID-induced gastric and duodenal ulcers and their complications. For list of factors that may increase the risk of NSAID-induced gastric and duodenal ulcers and their complications..
2 DOSAGE AND ADMINISTRATION
? Carefully consider the potential benefits and risks of ARTHROTEC and other treatment options before deciding to use ARTHROTEC. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals
? After observing the response to initial therapy with ARTHROTEC, the dose and frequency should be adjusted to suit an individual patient?s needs.
? For the relief of rheumatoid arthritis and osteoarthritis, the dosage is given below.
? ARTHROTEC is administered as ARTHROTEC 50 (50 mg diclofenac sodium/200 mcg misoprostol) or as ARTHROTEC 75 (75 mg diclofenac sodium/200 mcg misoprostol).
DOSAGE FORMS AND STRENGTHS
ARTHROTEC (diclofenac sodium/misoprostol) tablets:
50 mg/200 mcg tablet is round, biconvex, white to off-white imprinted with four ?A?s? encircling ?50? in the middle on one side and ?SEARLE? and ?1411? on the other.
75 mg/200 mcg tablet is round, biconvex, white to off-white imprinted with four ?A?s? encircling ?75? in the middle on one side and ?SEARLE? and ?1421? on the other.
