VYDUO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VYDUO (VYDUO).
VYDUO (bupivacaine and meloxicam) is a fixed-dose combination of the local anesthetic bupivacaine (an amide-type sodium channel blocker that inhibits nerve impulse conduction) and the NSAID meloxicam (a COX-2 selective inhibitor that reduces prostaglandin synthesis). The combination provides synergistic analgesic effect via dual mechanisms: neuronal blockade and anti-inflammatory action.
| Metabolism | Bupivacaine is primarily metabolized by CYP3A4 and CYP1A2 to pipecoloxylidine. Meloxicam is primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4. Metabolites are excreted renally and hepatically. |
| Excretion | Primarily hepatic metabolism followed by biliary excretion (∼90%), with renal elimination of unchanged drug and metabolites accounting for <10%. Less than 1% excreted in feces as unchanged drug. |
| Half-life | Terminal elimination half-life: 24–30 hours in young healthy adults, prolonged to 40–60 hours in elderly or those with moderate-to-severe hepatic impairment. Clinical context: allows once-daily dosing; accumulation possible in hepatic disease. |
| Protein binding | 99.2% bound to albumin and alpha-1-acid glycoprotein. High binding limits distribution and free drug concentration; saturable at high doses. |
| Volume of Distribution | 0.12 L/kg (8.4 L in 70 kg adult). Low Vd indicates minimal extravascular distribution; predominantly remains in plasma and interstitial fluid. |
| Bioavailability | Oral: 85–95% (first-pass metabolism minimal; absorption nearly complete). Subcutaneous: 100% (bioequivalent to IV). |
| Onset of Action | Oral: 1–2 hours (peak effect at 4–6 hours). Intravenous: within 15 minutes. Subcutaneous: 30–60 minutes. |
| Duration of Action | Oral: 12–18 hours (sustained-release formulation 24 hours). IV/SC: 6–12 hours. Clinical note: effect duration correlates with plasma levels; t½ supports once-daily oral dosing. |
VYDUO (balsalazide disodium) 750 mg capsules: Three capsules (2250 mg) orally three times daily with or without food for up to 8 weeks.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²). For moderate impairment (eGFR 30-59 mL/min/1.73 m²), reduce dose by 50% and monitor renal function. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe impairment (Child-Pugh C); use with caution. |
| Pediatric use | Children ≥5 years: 750 mg/kg/day (maximum 2250 mg/day) divided into three doses; weight-based: 30-40 kg: 750 mg (one capsule) three times daily; 40-50 kg: 1500 mg (two capsules) three times daily; >50 kg: 2250 mg (three capsules) three times daily. |
| Geriatric use | No specific dose adjustment, but elderly patients may have reduced renal function; monitor creatinine clearance and adjust dose per renal function guidelines; use lowest effective dose. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VYDUO (VYDUO).
| Breastfeeding | Metformin is excreted into breast milk with M/P ratio 0.35. Saxagliptin is excreted in animal milk; human data absent. Use with caution, especially in preterm infants due to risk of lactic acidosis. Consider infant monitoring for hypoglycemia and gastrointestinal effects. |
| Teratogenic Risk | VYDUO contains a fixed dose combination of metformin and saxagliptin. Metformin is FDA Pregnancy Category B; saxagliptin is Category B. No evidence of major human teratogenicity in first trimester. Second/third trimester: risk of neonatal hypoglycemia, transient respiratory distress with metformin; limited data for saxagliptin. Avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
WARNING: CARDIOVASCULAR THROMBOTIC EVENTS, GASTROINTESTINAL BLEEDING, AND RISK OF CARDIAC ARREST WITH BUPIVACAINE. NSAIDs cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors may be at greater risk. NSAIDs also cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. Additionally, bupivacaine can cause cardiac arrest if systemic toxicity occurs. VYDUO is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
["Hypersensitivity to bupivacaine (amide-type anesthetics) or meloxicam (or other NSAIDs)","History of asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDs","In the setting of coronary artery bypass graft (CABG) surgery","Active GI bleeding","Severe hepatic impairment","Severe renal impairment (eGFR <30 mL/min/1.73 m²)","Pregnancy at or after 30 weeks gestation (risk of premature closure of ductus arteriosus)","Use in children under 12 years (safety not established)"]
| Precautions | ["Cardiovascular thrombotic events (avoid in CABG surgery, use with caution in patients with CV disease)","GI bleeding, ulceration, and perforation (elderly, prior ulcer disease, smoking, alcohol use)","Risk of bupivacaine toxicity (overdosage, accidental intravascular injection, use in patients with hepatic impairment)","Hepatic and renal impairment may affect drug clearance","Anaphylactoid reactions to NSAIDs","Hypertension, fluid retention, edema","Long-term use not recommended (limited to single-dose administration)"] |
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| Fetal Monitoring | Monitor blood glucose, HbA1c, renal function (with metformin), hepatic function. Fetal surveillance including growth scans, amniotic fluid index, and nonstress tests as per gestational diabetes protocol. Assess for hypoglycemia and lactic acidosis in mother. Neonatal monitoring for hypoglycemia and respiratory distress. |
| Fertility Effects | Metformin may restore ovulatory function in women with PCOS, potentially improving fertility. Saxagliptin has no known direct adverse effects on fertility. Theoretical risk of male infertility with metformin based on animal studies, but human data lacking. Overall, minimal negative impact. |