SODIUM ZIRCONIUM CYCLOSILICATE Drug Interactions: What You Need to Know

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 [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 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 [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

None. None. ( 4 )

AND PRECAUTIONS

• Gastrointestinal Adverse Events in Patients with Motility Disorders. ( 5.1 )
• Edema. ( 5.2 )
• Hypokalemia in patients on hemodialysis. ( 5.3 )
• LOKELMA has radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures. ( 5.4 )

5.1 Gastrointestinal Adverse Events in Patients with Motility Disorders Avoid use of LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because LOKELMA has not been studied in patients with these conditions and may be ineffective and may worsen gastrointestinal conditions.

5.2 Edema Each 5 g dose of LOKELMA contains approximately 400 mg of sodium, but the extent of absorption by the patient is unknown. In clinical trials of LOKELMA in patients who were not on dialysis, edema was observed and was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (e.g., heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed <span class="opacity-50 text-xs">[see Adverse Reactions (6) ]</span> . In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups.

5.3 Hypokalemia in Patients on Hemodialysis Patients on hemodialysis may be prone to acute illness that can increase the risk of hypokalemia on LOKELMA (e.g., illnesses associated with decreased oral intake, diarrhea). Consider adjusting Lokelma dose based on potassium levels in these settings.

5.4 Diagnostic Tests LOKELMA has radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures .