ARTHROTEC

General Pharmacokinetic Characteristics The pharmacokinetic profiles of diclofenac and misoprostol administered as the fixed combination (ARTHROTEC 50 or 75) are similar to the profiles when the two drugs are administered as separate tablets (see Table 2 ). No pharmacokinetic interaction between the two drugs has been observed following multiple dosing. The diclofenac total exposure [area under the curve (AUC)] is dose-proportional within the range of 25 mg to 150 mg. Approximately dose-proporti...

Osteoarthritis Diclofenac sodium, as a single ingredient or in combination with misoprostol, has been shown to be effective in the management of the signs and symptoms of osteoarthritis. Rheumatoid Arthritis Diclofenac sodium, as a single ingredient or in combination with misoprostol, has been shown to be effective in the management of the signs and symptoms of rheumatoid arthritis. Upper Gastrointestinal Safety Diclofenac, and other NSAIDs, have caused serious gastrointestinal toxicity, such as bleeding, ulceration, and perforation of the stomach, small intestine or large intestine. Misoprost...

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) ]
• An...

ARTHROTEC is contraindicated in the following patients:

• Pregnancy. Use of misoprostol, a component of ARTHROTEC, 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 ...

• Embryo-Fetal Toxicity with NSAIDs : Use of NSAIDs, including diclofenac in women at about 20 weeks gestation and later in pregnancy may cause oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus. ( 4 , 5.1 , 8.1 )
• Hepatotoxicity : Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop. ( 5.4 )
• Hypertension : Patients taking some ...

7 DRUG INTERACTIONS See Table 1 for clinically significant drug interactions with diclofenac and misoprostol.

Table 1Clinically 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 incre...