Sodium zirconium cyclosilicate

What it is used for

Limitation of Use

LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

Side effects, and when to stop

The following adverse reactions are discussed in greater detail elsewhere in the label:

• Edema.

Who should not take it

None.

Other medicines and interactions

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. 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.

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 g in 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.

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