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. |
| Molecular Weight | 376.4 |
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 | Avoid use during first trimester due to risk of miscarriage and neural tube defects. May impair folic acid absorption. |
| 2nd trimester | Use only if clearly needed. Potential risk of fetal acidosis and growth restriction. |
| 3rd trimester | Avoid near term due to risk of premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for YOSPRALA (YOSPRALA).
| Placental transfer | Passes placenta; fetal serum levels are approximately 50-100% of maternal levels. |
| Breastfeeding | Compatible with breastfeeding. Use lowest effective dose. Metabolites and small amounts of parent drug transfer into milk, but no adverse effects reported in infants. |
| Lactation Rating |
■ 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 or omeprazoleHistory of asthma, urticaria, or allergic-type reactions after taking salicylatesSevere hepatic impairmentActive peptic ulcer disease or gastrointestinal bleedingCo-administration with nelfinavir or rilpivirine
| 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. |
| Food/Dietary | Take on an empty stomach at least 60 minutes before a meal. Avoid food that may increase gastric acid secretion (e.g., spicy, fatty, or acidic foods) as it can reduce efficacy. Alcohol may increase the risk of GI bleeding. No specific food contraindications, but maintain a balanced diet. Do not take with grapefruit juice, as it may interfere with esomeprazole metabolism. |
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| L2 (Safer) |
| 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. |
| 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. |
| Clinical Pearls | YOSPRALA is a fixed-dose combination of esomeprazole (40 mg) and aspirin (325 mg or 81 mg). It is used for the prevention of aspirin-induced gastric ulcers in patients at risk. The enteric-coated aspirin core is surrounded by an immediate-release esomeprazole layer, allowing pH-dependent release. Administer at least 60 minutes before a meal. Do not crush or chew. Monitor for GI bleeding, especially in elderly or those on anticoagulants. Avoid use in patients with severe hepatic impairment or those allergic to proton pump inhibitors or NSAIDs. |
| Patient Advice | Take YOSPRALA at least 60 minutes before a meal, preferably in the morning. · Swallow the tablet whole with water; do not crush, chew, or split. · This medication reduces the risk of stomach ulcers caused by aspirin but does not prevent all GI side effects. · Report any signs of bleeding, such as black stools, blood in vomit, or unusual bruising. · Avoid alcohol and NSAIDs (e.g., ibuprofen, naproxen) while taking this medication. · Inform your doctor if you have liver disease, osteoporosis, or low magnesium levels. · Do not stop taking YOSPRALA without consulting your doctor, as it may increase the risk of heart attack or stroke. · Store at room temperature, away from moisture and heat. |