NEXCEDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEXCEDE (NEXCEDE).
NEXCEDE is a combination of omeprazole (proton pump inhibitor) and naproxen (nonsteroidal anti-inflammatory drug). Omeprazole irreversibly inhibits the gastric H+/K+-ATPase pump, reducing gastric acid secretion. Naproxen inhibits cyclooxygenase (COX)-1 and COX-2, decreasing prostaglandin synthesis, which reduces inflammation, pain, and fever.
| Metabolism | Omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. Naproxen is metabolized in the liver primarily by CYP2C9. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 60% of the dose via glomerular filtration and tubular secretion). Biliary/fecal excretion accounts for about 30% of the dose. Less than 10% is metabolized. |
| Half-life | Terminal elimination half-life is approximately 8 hours in patients with normal renal function. This supports twice-daily dosing. In patients with renal impairment (CrCl <30 mL/min), half-life may extend to 15-20 hours, requiring dose adjustment. |
| Protein binding | Approximately 94% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 0.8 L/kg (range 0.5-1.2 L/kg), indicating distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is approximately 35% due to first-pass metabolism in the liver and intestinal wall. Bioavailability is not significantly affected by food. |
| Onset of Action | Intravenous administration: Onset of clinical effect (reduction of blood pressure) occurs within 5-10 minutes. Oral administration: Peak plasma concentrations reached at 1-2 hours, but antihypertensive effect begins within 2-4 hours. |
| Duration of Action | Duration of antihypertensive effect is approximately 12-16 hours after a single dose, allowing for twice-daily administration. Effect persists for up to 24 hours in some patients. |
50-100 mg orally twice daily, with or without food. Maximum 200 mg/day.
| Dosage form | FILM |
| Renal impairment | GFR 30-89 mL/min: 50 mg twice daily; GFR <30 mL/min: 50 mg once daily; dialysis: 50 mg once daily. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 50 mg twice daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | Start at 50 mg twice daily; may increase to 100 mg twice daily based on tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEXCEDE (NEXCEDE).
| Breastfeeding | No human data on excretion in breast milk. Cefovecin is highly protein-bound and has a large volume of distribution, suggesting minimal milk transfer. M/P ratio is unknown. Use with caution in nursing mothers due to potential for infant gut flora alteration. |
| Teratogenic Risk | NEXCEDE (cefovecin) is a veterinary cephalosporin antibiotic with no human pregnancy data. Based on animal studies, it is not associated with teratogenic effects, but risks in human pregnancy are unknown. In the absence of human data, it should be used in pregnancy only if clearly needed. First trimester risks are uncharacterized; second/third trimester risks are likely low but not established. |
■ FDA Black Box 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. NEXCEDE is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. NSAIDs cause an increased risk of serious gastrointestinal 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.
| Serious Effects |
History of allergic reaction to omeprazole, naproxen, or any component of the formulation; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; patients with moderate to severe renal impairment (CrCl <30 mL/min); patients with known hypersensitivity to proton pump inhibitors.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; renal toxicity; hepatic effects; hypertension; heart failure; anaphylactoid reactions; skin reactions; hematologic toxicity; masking of inflammation and fever; CYP2C9 poor metabolizers; concomitant use of NSAIDs; use with aspirin or anticoagulants; use with corticosteroids; use with diuretics; use in pregnancy; use in lactation; use in pediatric patients; use in elderly; renal impairment; hepatic impairment. |
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| Fetal Monitoring | No specific monitoring required. Standard obstetric monitoring is advised if used during pregnancy. |
| Fertility Effects | No human fertility studies. Animal studies show no significant adverse effects on fertility or reproductive performance. |