HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ARTHROTEC safely and effectively. See full prescribing information for ARTHROTEC.
ARTHROTEC® (diclofenac sodium and misoprostol tablets), for oral use
Initial U.S. Approval:1997
WARNING: RISK OF UTERINE RUPTURE, ABORTION, PREMATURE BIRTH, BIRTH DEFECTS; AND SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
See full prescribing information for complete boxed warning.
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 (4, 5.10, 8.1).
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 a negative serum pregnancy test within 2 weeks prior to beginning therapy (8.3).
- 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 Risk
- 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 (5.1).
- ARTHROTEC is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (4, 5.1).
Gastrointestinal Bleeding, Ulceration, and Perforation Risk
- 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 (5.2).
RECENT MAJOR CHANGES
|Indications and Usage (1)
|Dosage and Administration (2)
|Warnings and Precautions (5)
INDICATIONS AND USAGE
ARTHROTEC is a combination non-steroidal anti-inflammatory and prostaglandin E1 analog drug indicated for the treatment of signs and symptoms of osteoarthritis (OA) or rheumatoid arthritis (RA) in patients at high risk of developing NSAID-induced gastric and duodenal ulcers and their complications (1)
DOSAGE AND ADMINISTRATION
- Use the lowest effective dosage for shortest duration consistent with individual patient treatment goals (2)
- OA: 100 to 150 mg diclofenac/400 to 600 mcg misoprostol per day, divided for administration two or three times a day. Dose of diclofenac higher than 150 mg/day is not recommended (2)
- RA: 100 to 200 mg diclofenac/400 to 800 mcg misoprostol per day, divided for administration two, three or four times a day. Dose of diclofenac higher than 225 mg/day is not recommended (2)
DOSAGE FORMS AND STRENGTHS
ARTHROTEC (diclofenac/misoprostol) tablets: 50 mg/200 mcg and 75 mg/200 mcg (3)
- Known hypersensitivity to diclofenac, misoprostol or any components of the drug product (4)
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs (4)
- In the setting of CABG surgery (4)
- Pregnancy (4)
- Active gastrointestinal bleeding (4)
WARNINGS AND PRECAUTIONS
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 (5.3)
Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure (5.4, 7)
Heart Failure and Edema: Avoid use of ARTHROTEC in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure (5.5)
Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of ARTHROTEC in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function (5.6)
Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs (5.7)
Exacerbation of Asthma Related to Aspirin Sensitivity: ARTHROTEC is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity) (5.8)
Serious Skin Reactions: Discontinue ARTHROTEC at first appearance of skin rash or other signs of hypersensitivity (5.9)
Premature Closure of Fetal Ductus Arteriosus: Avoid use in pregnancy. Diclofenac may cause premature closure of the fetal ductus arteriosus. (5.10, 8.1)
Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia (5.11, 7)
Most common adverse reactions (incidence > 2% from clinical trials) are: abdominal pain, diarrhea, dyspepsia, nausea, flatulence, gastritis, vomiting, constipation, headache, dizziness, alanine aminotransferase increased, hematocrit decreased (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drugs that Interfere with Hemostasis (e.g. warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking ARTHROTEC with drugs that interfere with hemostasis. Concomitant use of ARTHROTEC and analgesic doses of aspirin is not generally recommended (7)
ACE inhibitors, Angiotensin Receptor Blockers (ARB), or Beta-Blockers: Concomitant use with ARTHROTEC may diminish the antihypertensive effect of these drugs. Monitor blood pressure (7)
ACE Inhibitors and ARBs: Concomitant use with ARTHROTEC in elderly, volume depleted, or those with renal impairment may result in deterioration of renal function. In such high risk patients, monitor for signs of worsening renal function (7)
Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects (7)
Digoxin: Concomitant use with ARTHROTEC can increase serum concentration and prolong half-life of digoxin. Monitor serum digoxin levels (7)
USE IN SPECIFIC POPULATIONS
Infertility: NSAIDs are associated with reversible infertility. Consider withdrawal of ARTHROTEC in women who have difficulties conceiving (8.3)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.