XARACOLL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XARACOLL (XARACOLL).
XARACOLL (bupivacaine and meloxicam) is a fixed-dose combination product for local analgesia. Bupivacaine is an amide local anesthetic that blocks sodium ion channels, inhibiting nerve impulse conduction. Meloxicam is an NSAID that inhibits cyclooxygenase (COX) isoforms, reducing prostaglandin synthesis.
| Metabolism | Bupivacaine undergoes hepatic metabolism via N-dealkylation and hydroxylation mediated primarily by CYP3A4 and CYP1A2. Meloxicam is extensively metabolized in the liver by CYP2C9 and CYP3A4. |
| Excretion | Primarily hepatic metabolism followed by renal excretion of metabolites; approximately 70-80% eliminated in urine (metabolites), <15% unchanged in feces via biliary excretion. |
| Half-life | Terminal elimination half-life is approximately 2-4 hours; clinical context: methadone-like opioid, prolonged half-life in elderly, renal impairment, or hepatic impairment; requires monitoring for accumulation. |
| Protein binding | Approximately 80-90%; primarily bound to alpha-1-acid glycoprotein and albumin; clinically relevant: displacement interactions possible but not common. |
| Volume of Distribution | Approximately 1.0-2.0 L/kg; extensive tissue distribution due to lipophilicity; clinical meaning: large Vd indicates high tissue binding; minimal effect of hemodialysis; reflects rapid redistribution. |
| Bioavailability | Buccal: approximately 70-80%; sublingual: approximately 70-80%; intravenous: 100% (not usually route); note: buccal avoids first-pass metabolism significantly. |
| Onset of Action | Buccal: 15-30 minutes; sublingual: 10-20 minutes; intravenous: morphine-like rapid onset (minutes) but not applicable; primary route buccal for acute pain; onset correlates with transmucosal absorption. |
| Duration of Action | Buccal/sublingual: 4-6 hours for analgesia; clinical notes: longer than IV morphine due to buccal route; duration may extend in hepatic impairment; acute pain management duration sufficient for procedural pain. |
| Molecular Weight | 446.5 |
Adults: Single dose of 1.3 g (two microspheres) applied intraoperatively directly to the subcutaneous tissue before wound closure.
| Dosage form | IMPLANT |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | No dose adjustment required for any degree of hepatic impairment, including Child-Pugh Class C. |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment recommended; use standard adult dosing. Clinical studies included patients aged 65 and older with no observed differences in safety or efficacy. |
| 1st trimester | Avoid use if possible; limited data, but NSAID use in first trimester may be associated with increased risk of miscarriage. |
| 2nd trimester | Use only if clearly needed and avoid prolonged use; NSAIDs may cause oligohydramnios and fetal renal impairment. |
| 3rd trimester | Contraindicated in third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for XARACOLL (XARACOLL).
| Placental transfer | Crosses the placenta; fetal concentrations may reach 30-50% of maternal levels. |
| Breastfeeding | Excretion into human milk is unknown; due to long half-life and potential for infant toxicity, avoid use or discontinue breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
Risk of cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal.
| Serious Effects |
Known hypersensitivity to ketorolac or other NSAIDsHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingAdvanced renal impairment (CrCl <30 mL/min) or risk of renal failureCerebrovascular bleeding, hemorrhagic diathesis, or incomplete hemostasisConcomitant use of probenecidConcomitant use of other NSAIDs including aspirin in full doseLabor or deliveryThird trimester pregnancy
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; hepatotoxicity; hypertension; heart failure; renal toxicity; anaphylactoid reactions; serious skin reactions; fetal toxicity; hematologic toxicity; pre-existing asthma; ophthalmic effects; and use in labor and delivery. |
| Food/Dietary |
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| L5 - Contraindicated |
| Teratogenic Risk | Fetal risk cannot be ruled out. XARACOLL (bupivacaine and meloxicam) is not recommended during pregnancy. Bupivacaine crosses the placenta; meloxicam, as an NSAID, is associated with premature closure of the ductus arteriosus and oligohydramnios in the third trimester. Avoid use after 30 weeks gestation. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and signs of bleeding. In third-trimester use, monitor fetal ductus arteriosus via ultrasound and amniotic fluid volume. Assess infant for respiratory depression if used near term. |
| Fertility Effects | Meloxicam may impair female fertility via prostaglandin-mediated effects on ovulation; reversible upon discontinuation. Bupivacaine has no known direct fertility effects. |
| No specific food interactions have been reported for XARACOLL. However, grapefruit juice may theoretically inhibit CYP3A4-mediated metabolism of bupivacaine, potentially increasing systemic exposure; consider avoiding grapefruit products. |
| Clinical Pearls | XARACOLL (bupivacaine collagen-matrix implant) is indicated for surgical-site analgesia. It is placed intraoperatively into the surgical wound. Do not use in patients with known hypersensitivity to amide anesthetics. Avoid concomitant use with Class III antiarrhythmics (e.g., amiodarone). Maximum plasma concentrations peak at 1-2 hours post-implantation; monitor for CNS and cardiac toxicity. Not for use in neuraxial anesthesia or intravascular injection. Each implant provides up to 24 hours of local analgesia. |
| Patient Advice | XARACOLL is a medication placed directly into the surgical wound during your operation to provide pain relief for about 24 hours. · You may still receive other pain medications as needed; XARACOLL does not replace all pain management. · Report any signs of allergic reaction such as rash, itching, swelling, or difficulty breathing immediately. · Numbness or tingling beyond the surgical site, dizziness, or irregular heartbeat should be reported to your healthcare provider. · Avoid driving or operating heavy machinery until you know how the medication affects you, as it may cause drowsiness or dizziness. |