Yosprala(TM) in At-Risk Patients Requiring Low-Dose Aspirin

Question

Do the benefits of Yosprala^™ therapy outweigh its costs when compared with combination therapy with aspirin and a proton-pump inhibitor taken as individual products?

Response from Devada Singh-Franco, PharmD
Associate Professor, Department of Pharmacy Practice, Nova Southeastern University College of Pharmacy; Ambulatory Care Pharmacist, Broward Health Medical Center, Fort Lauderdale, Florida

Patients at risk for cardiovascular (CV) events who are prescribed low-dose aspirin (LDA, ≤ 325 mg/day) may become nonadherent to therapy due to reflux symptoms and abdominal pain.^[1] Unfortunately, nonadherence can increase the risk for CV events, including death.^[2] Clinical research shows that continuous proton-pump inhibitor (PPI) use significantly reduces the risk for LDA discontinuation in patients at high risk for a gastrointestinal (GI) event.^[3] Despite this evidence, patients who receive LDA and are at increased risk for a GI event may not be prescribed gastroprotective therapy with a PPI or may not be regular PPI users.^[4] A PPI is recommended in patients receiving LDA for vascular protection if one of the following is present: history of nonbleeding ulcer disease; history of ulcer complication (ie, bleeding or perforation); dual-antiplatelet therapy; or concomitant anticoagulant therapy.^[5] In patients who do not meet the criteria above, a PPI is recommended if more than one of the following is present: age ≥60 years; corticosteroid use; and/or dyspepsia or gastroesophageal reflux disease (GERD) symptoms.^[5] This article will review the role of Yosprala^™in patients requiring LDA and PPI therapy and determine whether the benefits of this fixed-dose combination outweigh the costs when compared to aspirin with or without a PPI.

Indication

Yosprala, a fixed-dose combination of aspirin (an antiplatelet agent) and omeprazole (a PPI), recently received approval by the US Food & Drug Administration for use in patients who require aspirin for secondary prevention of CV and cerebrovascular events and who are at risk of developing aspirin-associated gastric ulcers due to age (≥ 55 years) or documented history of gastric ulcer.^[6] The single tablet contains prescription-strength omeprazole (40 mg immediate-release formulation) with either 81 mg or 325 mg delayed-release aspirin. Yospralais not interchangeable with the individual components of aspirin and omeprazole.^[6]

Pharmacodynamics/Pharmacokinetics

Yosprala'sproprietary formulation is designed to sequentially deliver immediate-release omeprazole (to increase gastric pH), followed by enteric-coated delayed-release aspirin (EC-ASA). The EC-ASA core is surrounded by a pH-sensitive coating, and the immediate-release omeprazole is embedded in a film coat in the outer layer of the tablet for instantaneous dissolution.^[7] Aspirin is released only after GI tract pH is >5.5.^[7]

Because omeprazole is the immediate-release preparation in Yosprala, it has a quicker onset of action but remains vulnerable to degradation by low gastric pH. The percent time with gastric pH > 4 over 24 hours with Yosprala versus enteric-coated omeprazole 40 mg was 50.6% versus 57.6% (P = .004), respectively.^[7] While no head-to-head comparisons are available, duration of intragastric pH > 4 by Yosprala appears similar to that of enteric-coated omeprazole 20 mg (48.7%),^[8] which has been shown to be effective in the prevention and treatment of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage.^[9]

With immediate-release or chewable aspirin, peak plasma levels can be achieved within 30-40 minutes postingestion.^[10,11] However, as the aspirin component of Yosprala is a delayed-release formulation, with peak concentrations reached in 2.5 hours for the 81-mg dose and 4-4.5 hours for the 325-mg dose, it should not be used as the initial dose of aspirin therapy during onset of acute coronary syndrome or acute myocardial infarction or before percutaneous coronary intervention, for which immediate-release aspirin therapy is appropriate.^[6]

While food has no effect on aspirin absorption, administration of Yosprala 60 minutes prior to a high-fat meal reduced omeprazole absorption by 15% compared with administration during fasting conditions.^[6] Therefore, the tablet should be administered at least 1 hour prior to a meal and is to be swallowed whole (no crushing, splitting, or chewing).

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