Bravo

Serious Warnings

• Black Box Warning: WARNING: RISK OF UTERINE RUPTURE, ABORTION, PREMATURE BIRTH, BIRTH DEFECTS; AND SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS. DICLOFENAC SODIUM AND MISOPROSTOL DELAYED-RELEASE TABLETS CONTAIN DICLOFENAC SODIUM AND MISOPROSTOL. ADMINISTRATION OF MISOPROSTOL TO WOMEN WHO ARE PREGNANT CAN CAUSE ABORTION, PREMATURE BIRTH, BIRTH DEFECTS, OR UTERINE RUPTURE. UTERINE RUPTURE HAS BEEN REPORTED WHEN MISOPROSTOL WAS ADMINISTERED IN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION. This drug also carries a risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Additionally, NSAIDs cause an increased risk of serious gastrointestinal 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.
• 1.
• **Pregnancy and Reproductive Health:** This drug is absolutely contraindicated in pregnant women due to the severe risk of abortion, premature birth, birth defects, and uterine rupture associated with misoprostol.
• Pre-menopausal women of childbearing potential must use effective contraception during treatment and should not initiate therapy if planning pregnancy.
• Not safe for use during breastfeeding; consult a physician.
• 2.
• **Cardiovascular Risk:** Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal.
• These events may occur early in treatment and increase with duration of use.
• Contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
• Can cause new onset or worsening hypertension, fluid retention, and edema, potentially exacerbating heart failure.
• Use with caution in patients with cardiac insufficiency, cerebrovascular, coronary, or peripheral artery disease.
• 3.
• **Gastrointestinal Risk:** Increased risk of serious GI bleeding, ulceration, and perforation, which can be fatal.
• These events can occur at any time during use without warning symptoms.
• Use with extreme caution in patients with a history of gastric lesions or active peptic ulcers.
• 4.
• **Hepatotoxicity:** Can cause elevations in liver enzymes and, in rare cases, severe and sometimes fatal liver reactions, including fulminant hepatitis, liver necrosis, and hepatic failure.
• Regular monitoring of liver function tests is advised, especially in elderly patients and those on long-term therapy.
• 5.
• **Renal Toxicity and Hyperkalemia:** Can cause renal papillary necrosis and other renal injury.
• Use with caution in patients with renal insufficiency.
• May also lead to hyperkalemia.
• 6.
• **Hypersensitivity/Allergy:** Severe, sometimes fatal, anaphylactic reactions and serious skin reactions (e.
• g.
• , Stevens-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis) have been reported.
• Contraindicated in patients with known hypersensitivity to diclofenac, misoprostol, other prostaglandins, or any components, and in those with a history of asthma, urticaria, or other allergic-type reactions to aspirin or other NSAIDs.
• 7.
• **Hematologic Toxicity:** Can cause anemia and other hematologic abnormalities.
• Regular monitoring of blood tests is advised, especially in elderly patients and those on long-term therapy.
• 8.
• **General Precautions:** Carefully consider the potential benefits and risks.
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
• In elderly patients and those receiving long-term therapy, liver function tests and blood tests must be regularly monitored.