⛔ FDA Black Box Warning
WARNING: RISK OF SERIOUS CARDIOVASCULAR and GASTROINTESTINAL EVENTS WARNING: RISK OF SERIOUS CARDIOVASCULAR and GASTROINTESTINAL EVENTS See full prescribing information for complete boxed warning. 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 the treatment and may increase with duration of use ( 5.1 ) LICART is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. ( 4 , 5.1 ) 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 ) 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 [See Warnings and Precautions (5.1) ] . LICART is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [See Contraindications (4) and Warnings and Precautions (5.1) ]. 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 [See Warnings and Precautions (5.2) ] .
Contraindications
4 CONTRAINDICATIONS LICART is contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [see Warnings and Precautions (5.7 , 5.9) ]. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7 , 5.8) ]. In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1) ]. On non-intact or damaged skin resulting from any etiology, including exudative dermatitis, eczema, infected lesions, burns or wounds. Known hypersensitivity to diclofenac or any components of the drug product ( 4 ) History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs ( 4 ) In the setting of CABG surgery ( 4 ) For use on non-intact or damaged skin ( 4 )
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Use of NSAIDs, including LICART, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of LICART use between about 20 and 30 weeks of gestation, and avoid LICART use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations and Data ). Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including LICART, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, diclofenac epolamine administered orally to pregnant rats and rabbits during the period of organogenesis produced embryotoxicity at approximately 3 and 7 times, respectively, the topical exposure from the maximum recommended human dose (MRHD) of LICART. In rats, increased incidences of skeletal anomalies and maternal toxicity were also observed at this dose. Diclofenac epolamine administered orally to both male and female rats prior to mating and throughout the mating period, and during gestation and lactation in females produced embryotoxicity at doses approximately 3 and 7 times, respectively, the topical exposure from the MRHD (see Data ) . Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in incre