lokelma

Recommended starting dose is 10 g administered three times a day for up to 48 hours. ( 2.1 ) • For maintenance treatment, recommended dose is 10 g once daily. Adjust dose at one-week intervals as needed (by 5 g daily) to obtain desired serum potassium target range. ( 2.1 ) Patients on Chronic Hemodialysis • Recommended starting dose is 5 g once daily on non-dialysis days. ( 2.2 ) See full Prescribing Information for additional dosing instructions, as well as reconstitution and administration instructions for the oral suspension. 2.1 Recommended Dosage For initial treatment of hyperkalemia, the recommended dose of LOKELMA is 10 g administered three times a day for up to 48 hours. Administer LOKELMA orally as a suspension in water [see Dosage and Administration (2.3) ] . For continued treatment, the recommended dose is 10 g once daily. Monitor serum potassium and adjust the dose of LOKELMA based on the serum potassium level and desired target range. During maintenance treatment, up-titrate based on the serum potassium level at intervals of 1-week or longer and in increments of 5 g. Decrease the dose of LOKELMA or discontinue if the serum potassium is below the desired target range. The recommended maintenance dose range is from 5 g every other day to 15 g daily. 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis For patients on chronic hemodialysis, administer LOKELMA…

The following adverse reactions are discussed in greater detail elsewhere in the label: • Edema [see Warnings and Precautions (5.2) ] . Most common adverse reactions with LOKELMA: mild to moderate edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The total exposure to LOKELMA in the safety and efficacy clinical trials of patients not on dialysis with hyperkalemia was 1,760 patients with 652 patients exposed to LOKELMA for at least 6 months and 507 patients exposed for at least one year. The population (n=1,009) in the placebo-controlled trials included patients aged 22 to 96 years, females (n=454), Caucasians (n=859) and Blacks (n=130). Patients had hyperkalemia in association with comorbid diseases such as chronic kidney disease, heart failure, and diabetes mellitus. In placebo-controlled trials in which patients who were not on dialysis were treated with once daily doses of LOKELMA for up to 28 days, edema was reported in 4.4% of patients receiving 5 g, 5.9% of patients receiving 10 g and…

None. None. ( 4 )

LOKELMA can transiently increase gastric pH. As a result, LOKELMA can change the absorption of co-administered drugs that exhibit pH-dependent solubility, potentially leading to altered efficacy or safety of these drugs when taken close to the time LOKELMA is administered. In general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ] . LOKELMA is not expected to impact systemic exposure of drugs that do not exhibit pH-dependent solubility and so spacing is not needed if it has been determined that the concomitant medication does not exhibit pH-dependent solubility. In general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA. ( 2.3 , 7 , 12.3 ) Drug Interactions Thirty-six (36) drugs were tested in-vitro to determine potential interactions with LOKELMA. Sixteen (16) drugs tested did not show an in vitro interaction with LOKELMA (allopurinol, apixaban, aspirin, captopril, cyclosporine, digoxin, ethinyl estradiol, lisinopril, magnesium, metformin, phenytoin, prednisone, propranolol, quinapril, spironolactone and ticagrelor). Nine (9) of the 20 drugs that showed an in vitro interaction were subsequently tested in vivo with LOKELMA 10 gin healthy volunteers. Losartan, glipizide and levothyroxine did not show any changes in exposure when co-administered with LOKELMA. However, there was an increase in systemic exposure to weak acids such as furosemide and atorvastatin, and a decrease in systemic exposure to weak bases such as dabigatran when co-administered with LOKELMA, as shown in Figure 2. These changes are consistent with the hypothesis that LOKELMA, by elevating gastric pH, affects the systemic exposure of co-administered drugs whose solubility is pH-dependent [see Drug Interactions (7) ] . In another drug-drug interaction study in healthy volunteers, co-administration of LOKELMA 15 g decreased the systemic exposures of tacrolimus (Figure 2), likely due to LOKELMA’s action on elevating gastric pH. In the same study, co-administration of LOKELMA and cyclosporine did not show a clinically meaningful interaction. Figure 2: Effects of LOKELMA 10 g or 15 g on the Pharmacokinetic Exposures of Other Orally Administered Medications figure_2