Dosages: EQ 20MG BASE; EQ 20MG BASE/PACKET; EQ 40MG BASE; EQ 40MG BASE/PACKET
Market Status: Prescription
Active Ingredients: Esomeprazole Magnesium
Drug Form: Capsule, Delayed Rel Pellets; Oral; For Suspension, Delayed Release; Oral
Year Approved: 2001
Company Name: Astrazeneca
The active ingredient in NEXIUM (esomeprazole magnesium) Delayed-Release Capsules is bis( 5-methoxy-2-[( S)-[( 4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl] sulfinyl]-1H-benzimidazole-1-yl) magnesium trihydrate, a compound that inhibits gastric acid secre-tion. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S-and R-isomers. Its empirical formula is (C17 H18N3O3S) 2 Mg x 3 H2O with molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis.
The magnesium salt is a white to slightly colored crystalline powder. It contains 3 moles of water of solvation and is slightly soluble in water. The stability of esomeprazole magnesium is a function of pH; it rapidly degrades in acidic media, but it has acceptable stability under alkaline conditions. At pH 6.8 (buffer), the half-life of the magnesium salt is about 19 hours at 25 C and about 8 hours at 37 C.
NEXIUM is supplied as Delayed-Release Capsules for oral administration. Each delayed-release capsule contains 20 mg or 40 mg of esomeprazole (present as 22.3 mg or 44.5 mg esomeprazole magne-sium trihydrate) in the form of enteric-coated pellets with the following inactive ingredients: glyceryl monostearate 40-50, hydroxy-propyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, talc, and triethyl citrate. The capsule shells have the following inactive ingredients: gelatin, FD& C Blue #1, FD& C Red #40, D& C Red #28, titanium dioxide, shellac, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, propylene glycol, sodium hydroxide, polyvinyl pyrrolidone, and D& C Yellow #10.
Esomeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4. In vitro and in vivo studies have shown that esomeprazole is not likely to inhibit CYPs 1A2, 2A6, 2C9, 2D6, 2E1 and 3A4. No clinically rele-vant interactions with drugs metabolized by these CYP enzymes would be expected. Drug interaction studies have shown that esomeprazole does not have any clinically significant interactions with phenytoin, warfarin, quinidine, clarithromycin or amoxicillin.
Post-marketing reports of changes in prothrombin measures have been received among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Esomeprazole may potentially interfere with CYP2C19, the major esomeprazole metabolizing enzyme. Co-administration of esomepra-zole 30 mg and diazepam, a CYP2C19 substrate, resulted in a 45% decrease in clearance of diazepam. Increased plasma levels of diazepam were observed 12 hours after dosing and onwards. However, at that time, the plasma levels of diazepam were below the therapeutic interval, and thus this interaction is unlikely to be of clinical relevance.
Esomeprazole inhibits gastric acid secretion. Therefore, esomepra-zole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts and digoxin).
Coadministration of oral contraceptives, diazepam, phenytoin, or quinidine did not seem to change the pharmacokinetic profile of esomeprazole.