YOSPRALA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YOSPRALA (YOSPRALA).
Yosprala is a combination of aspirin (a nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase-1 and cyclooxygenase-2, thereby reducing thromboxane A2 synthesis and platelet aggregation) and omeprazole (a proton pump inhibitor that inhibits gastric acid secretion by binding to the H+/K+ ATPase enzyme in gastric parietal cells).
| Metabolism | Aspirin undergoes hydrolysis to salicylic acid primarily by esterases in the liver and plasma; omeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. |
| Excretion | YOSPRALA (esomeprazole and naproxen) is a fixed-dose combination. Naproxen is primarily excreted in urine as unchanged drug (approximately 60%) and as glucuronide conjugates (approximately 30%). Esomeprazole is extensively metabolized; less than 1% of the dose is excreted unchanged in urine. Biliary/fecal elimination accounts for the remainder via metabolites. |
| Half-life | Naproxen: terminal elimination half-life is approximately 14 hours (range 12–17 hours), allowing twice-daily dosing. Esomeprazole: terminal half-life is approximately 1.2–1.5 hours after single dose, increasing to ~1.5–2.5 hours with repeated dosing due to saturation of CYP2C19. Clinical context: naproxen's half-life supports sustained analgesic/anti-inflammatory effect; esomeprazole's shorter half-life requires daily dosing for acid suppression. |
| Protein binding | Naproxen: >99% bound to albumin. Esomeprazole: approximately 97% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Naproxen: apparent volume of distribution (Vd) is approximately 0.16 L/kg, indicating distribution primarily into extracellular fluid with limited tissue binding. Esomeprazole: Vd is approximately 0.22 L/kg, suggesting distribution into total body water. |
| Bioavailability | Naproxen: oral bioavailability is approximately 95%. Esomeprazole: oral bioavailability is approximately 50–60% after single dose, increasing to 60–70% with repeat dosing due to decreased first-pass metabolism; a delayed-release formulation (enteric-coated) is used in YOSPRALA. |
| Onset of Action | Naproxen: onset of analgesic effect is within 1 hour after oral administration. Esomeprazole: acid suppression begins within 1 hour; maximal effect on intragastric pH occurs after 4–5 days of dosing. |
| Duration of Action | Naproxen: analgesic/anti-inflammatory effect persists for up to 12 hours, supporting twice-daily dosing. Esomeprazole: acid suppression lasts approximately 24 hours with once-daily dosing; the duration of gastric acid reduction is sufficient for gastric mucosal protection. |
YOSPRALA (esomeprazole magnesium and naproxen) is available as delayed-release tablets containing 375 mg naproxen/20 mg esomeprazole or 500 mg naproxen/20 mg esomeprazole. The typical adult dose is one tablet twice daily, swallowed whole with liquid, at least 30 minutes before meals.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | Contraindicated in patients with estimated GFR <30 mL/min/1.73 m². For GFR 30-59 mL/min/1.73 m², the maximum naproxen dose is 500 mg/day; use YOSPRALA 375/20 twice daily (total naproxen 750 mg/day exceeds this limit, so avoid use or use alternative). No dose adjustment for GFR ≥60 mL/min. |
| Liver impairment | Child-Pugh Class A or B: No adjustment required. Child-Pugh Class C: Contraindicated due to naproxen component (severe hepatic impairment). |
| Pediatric use | Not approved for use in pediatric patients (<18 years); safety and efficacy not established. |
| Geriatric use | In patients ≥65 years, use the lowest effective dose and for the shortest duration. Avoid YOSPRALA in patients ≥65 years due to increased risk of cardiovascular and gastrointestinal adverse events from naproxen. If used, limit naproxen dose to 500 mg/day and consider monitoring renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for YOSPRALA (YOSPRALA).
| Breastfeeding | Naproxen and esomeprazole are excreted in human milk in low amounts. Naproxen has an M/P ratio of approximately 0.01, indicating minimal transfer. Esomeprazole has limited data but is poorly bioavailable orally. Caution is advised; consider the benefits of breastfeeding and the potential for adverse effects (e.g., GI upset, bleeding tendency). |
| Teratogenic Risk | FDA Pregnancy Category B. Based on animal reproduction studies and human data, YOSPRALA (esomeprazole and naproxen) is generally considered low risk for teratogenicity. However, naproxen is a nonsteroidal anti-inflammatory drug (NSAID) and may cause premature closure of the ductus arteriosus if used during the third trimester. Additionally, NSAID use in late pregnancy is associated with oligohydramnios, fetal renal dysfunction, and bleeding risks. Therefore, avoid use in the third trimester. |
■ FDA Black Box Warning
Reye's syndrome risk with aspirin use in children with viral infections; GI bleeding risk due to aspirin; potential for increased cardiovascular risk with co-administration of clopidogrel and omeprazole.
| Serious Effects |
Hypersensitivity to aspirin, omeprazole, or other PPIs; history of asthma, rhinitis, or nasal polyps precipitated by NSAIDs; bleeding disorders (e.g., hemophilia); active peptic ulcer disease; severe hepatic impairment; concomitant use of rilpivirine; children and adolescents with viral infections (Reye's syndrome risk).
| Precautions | Increased risk of GI bleeding (including hemorrhage, perforation, obstruction); renal impairment; anaphylactic reactions; bleeding disorders; interaction with clopidogrel leading to reduced antiplatelet effect; hypomagnesemia with prolonged PPI use; increased risk of Clostridium difficile infection; bone fracture risk with long-term PPI therapy; masking of gastric malignancy symptoms. |
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| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios and ductus arteriosus patency if used in the third trimester. Monitor maternal renal function, blood pressure, and signs of bleeding. In neonates, observe for respiratory depression, feeding difficulties, and bruising. |
| Fertility Effects | Naproxen may reversibly impair female fertility via inhibition of prostaglandin synthesis, affecting ovulation. This effect is dose-dependent and resolves upon discontinuation. No known effect on male fertility. |