Bupivacaine And Meloxicam

⛔ 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 treatment and may increase with duration of use ( 5.1 ) ZYNRELEF 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) ] . ZYNRELEF 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 ZYNRELEF is contraindicated in: Patients with a known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to any local anesthetic agent of the amide-type, NSAIDs, or to any of the other components of ZYNRELEF [see Warnings and Precautions (5.9 , 5.14) ] . Patients with a 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 (5.9) ] . Patients undergoing obstetrical paracervical block anesthesia. The use of bupivacaine in this technique has resulted in fetal bradycardia and death [see Use in Specific Populations (8.1) ] . Patients undergoing coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1) ] . ZYNRELEF is contraindicated for: Patients with a known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to any local anesthetic agent of the amide-type, NSAIDs, or to any of the other components of ZYNRELEF ( 4 ) Patients with a 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 ( 4 ) Patients undergoing obstetrical paracervical block anesthesia ( 4 ) Patients undergoing coronary artery bypass graft (CABG) surgery ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary There are no available human data on use of ZYNRELEF in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. However, there are available data on the individual components of ZYNRELEF, bupivacaine and meloxicam. Bupivacaine The available data on bupivacaine use in pregnant women for epidural anesthesia (excluding paracervical block) are insufficient to draw conclusions about a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are no adequate and well-controlled studies with bupivacaine in pregnant women. In animal studies, embryo-fetal lethality was noted when bupivacaine was administered subcutaneously to pregnant rabbits during organogenesis at a comparable bupivacaine dose level of 400 mg at the maximum recommended human dose (MRHD) of ZYNRELEF. Decreased pup survival was observed in a rat pre- and post-natal developmental study (dosing from implantation through weaning) at a comparable bupivacaine dose to the MRHD ( see Data ). Based on animal data, pregnant women should be advised of the potential risks to a fetus. Meloxicam Use of NSAIDs, including ZYNRELEF, 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 ZYNRELEF use between about 20 and 30 weeks of gestation and avoid ZYNRELEF use at about 30 weeks of gestation and later in pregnancy ( see Clinical Considerations , Data ). Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including ZYNRELEF, 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 ol