Cardiovascular Thrombotic Events
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
ZORVOLEX, TIVORBEX, and VIVLODEX are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
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.
ZORVOLEX, TIVORBEX, and VIVLODEX are contraindicated in patients with: a known hypersensitivity to the respective active ingredient (diclofenac, indomethacin or meloxicam) or their inactive ingredients; a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.
ZORVOLEX, TIVORBEX, or VIVLODEX should be used at the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
Elevation of one or more liver tests may occur during therapy with NSAIDs. Rare, sometimes fatal, cases of severe hepatic injury have been reported. Physicians should measure transaminases before starting and periodically during long-term treatment with ZORVOLEX. ZORVOLEX, TIVORBEX, or VIVLODEX should be discontinued immediately if clinical signs and symptoms of liver disease develop.
NSAIDs, including ZORVOLEX, TIVORBEX, and VIVLODEX, can lead to the new onset of hypertension or worsening of preexisting hypertension, which may contribute to the increased incidence of CV events. Blood pressure should be monitored during treatment with ZORVOLEX, TIVORBEX, or VIVLODEX. NSAIDs may diminish the antihypertensive activity of loop and thiazide diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers.
NSAID use has been associated with an increase in the risk of MI, hospitalizations due to heart failure, and death. Also, fluid retention and edema have been observed in patients taking NSAIDs. Avoid the use of ZORVOLEX, TIVORBEX, or VIVLODEX in patients with severe heart failure.
Long-term administration of NSAIDs can result in renal papillary necrosis and other renal injury. ZORVOLEX, TIVORBEX, or VIVLODEX should be used with caution in patients at greatest risk of this reaction, including the elderly, those with impaired renal function, heart failure, liver dysfunction, dehydration, hypovolemia, and those taking diuretics, ACE inhibitors, or ARBs. Avoid the use of NSAIDs in patients with advanced renal disease. Increases in serum potassium levels, including hyperkalemia, have been reported with NSAID use.
Anaphylactic reactions may occur in patients with the aspirin triad or in patients without prior exposure to ZORVOLEX, TIVORBEX, or VIVLODEX. These NSAIDs should be discontinued immediately if an anaphylactic reaction occurs.
NSAIDs can cause serious skin adverse events such as exfoliative dermatitis, Stevens - Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. ZORVOLEX, TIVORBEX, or VIVLODEX should be discontinued if rash or other signs of local skin reaction occur.
Indomethacin may aggravate depression, and other psychiatric disturbances, epilepsy, or parkinsonism, and should be used with caution in patients with these conditions. Indomethacin may cause drowsiness; therefore patients should be cautioned about engaging in activities requiring mental alertness and motor coordination. Discontinue TIVORBEX if severe central nervous system (CNS) adverse reactions develop.
Corneal deposits and retinal disturbances have been observed after prolonged therapy with indomethacin. Periodic ophthalmologic examinations are advisable in patients receiving prolonged therapy. TIVORBEX is not indicated for long-term treatment.
Starting at 30 weeks of gestation, NSAIDs, including ZORVOLEX, TIVORBEX and VIVLODEX, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur.
Concomitant administration of anticoagulants, antiplatelet agents (e.g., aspirin), SSRIs, SNRIs, salicylates, or other NSAIDs with ZORVOLEX, TIVORBEX, or VIVLODEX may increase the risk of bleeding.
The anti-inflammatory and anti-pyretic activity of ZORVOLEX, TIVORBEX, or VIVLODEX may mask the signs of infection.
Since serious GI, hepatic, and renal events have been reported with NSAID use, consider monitoring CBC and chemistry profile in patients on long-term NSAID therapy.
Most common adverse reactions (incidence ≥2%) in clinical trials with ZORVOLEX include: edema, nausea, headache, dizziness, vomiting, constipation, pruritus, diarrhea, flatulence, pain in extremity, abdominal pain, sinusitis, alanine aminotransferase increased, blood creatinine increased, hypertension, and dyspepsia.
Most common adverse reactions (incidence ≥2%) in clinical trials with TIVORBEX include: nausea, post procedural edema, headache, dizziness, vomiting, post procedural hemorrhage, constipation, pruritus, diarrhea, dyspepsia, post procedural swelling, presyncope, rash, upper abdominal pain, somnolence, generalized pruritus, hyperhidrosis, decreased appetite, hot flush, and syncope.
Most common adverse reactions (incidence ≥2%) in clinical trials with VIVLODEX include: diarrhea, nausea, and abdominal discomfort.
ZORVOLEX, TIVORBEX, or VIVLODEX capsules do not result in an equivalent systemic exposure to other formulations of oral diclofenac, indomethacin, or meloxicam, respectively. Therefore, do not substitute similar dose strengths of other: diclofenac products for ZORVOLEX; indomethacin products for TIVORBEX; or meloxicam products for VIVLODEX.
Please see accompanying full Prescribing Information for additional important safety and dosing information for ZORVOLEX, TIVORBEX, or VIVLODEX.