DRUG INTERACTIONS-

In general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA. 

BRIEF SUMMARY

12/18. SODIUM ZIRCONIUM CYCLOSILICATE- (May 2018)

Indn-   To treat hyperkalemia

Comp-  • For oral suspension: 5 g per packet                                                                       • Recommended starting dose is 10 g administered three times a day for up to 48 hours.  • 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. 

ADR- Most common adverse reactions with LOKELMA: mild to moderate edema.  

CI-  None. 

 WARNINGS -                                                                                                                       ­ • Gastrointestinal Adverse Events in Patients with Motility Disorders.                                • Edema. 

Pat inform-                                                                                                                  Inform the patient that it is necessary to drink the full dose                                              Drug Interactions                                                                                                          Advise patients who are taking other oral medications to separate dosing of LOKELMA by at least 2 hours (before or after)                                                                                  Diet                                                                                                                                Advise patients to adjust dietary sodium, if appropriate ..

=================================================================

U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  12

 ADVERSE REACTIONS-

Most common adverse reactions with LOKELMA: mild to moderate edema.  

 CONTRAINDICATIONS     

  None. 

 WARNINGS AND PRECAUTIONS

­ • Gastrointestinal Adverse Events in Patients with Motility Disorders.

 • Edema. 

 PATIENT COUNSELING INFORMATION

Dosing Instruct the patient how to reconstitute LOKELMA for administration.

Inform the patient that it is necessary to drink the full dose 

Drug Interactions

Advise patients who are taking other oral medications to separate dosing of LOKELMA by at least 2 hours (before or after) 

Diet                                                                                                                                Advise patients to adjust dietary sodium, if appropriate ..

Manufactured by:

AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

CLINICAL PHARMACOLOGY

1 Mechanism of Action

LOKELMA (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. In vitro, LOKELMA has a high affinity for potassium ions, even in the presence of other cations such as calcium and magnesium.

LOKELMA increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, thereby lowering serum potassium levels.

.2. Pharmacodynamics

In a study in healthy adult subjects, LOKELMA administered as 5 g or 10 g once daily for four days caused a dosedependent increase in fecal potassium excretion. Corresponding dose-dependent decreases in urinary potassium excretion and serum potassium were also observed.

 In patients with hyperkalemia treated with LOKELMA 10 g three times a day for up to 48 hours, reductions in serum potassium were observed one hour after initiation of therapy; serum potassium concentrations continued to decline over the 48-hour treatment period 

In patients not continuing LOKELMA, potassium levels increased. Patients with higher starting serum potassium levels or receiving a higher dose have greater reductions in serum potassium.

LOKELMA causes a small dose-dependent increase in serum bicarbonate concentrations (1.1 mmol/L at 5 g once daily, 2.3 mmol/L at 10 g once daily and 2.6 mmol/L at 15 g once daily as compared with a mean increase of 0.6 mmol/L in patients treated with placebo). The clinical significance of this finding is unclear.

3. Pharmacokinetics-                                                                                           LOKELMA is an inorganic, insoluble compound that is not subject to enzymatic metabolism.

In a clinical study in patients with hyperkalemia in which zirconium concentrations were measured in the urine and blood, zirconium concentrations were similar in treated and untreated patients (i.e., either undetectable or around the lower limit of quantification of the assay).

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

LOKELMA is not absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug.

2.Lactation Risk Summary

LOKELMA is not absorbed systemically following oral administration, and breastfeeding is not expected to result in exposure of the child to LOKELMA. 

3. Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

4.Geriatric Use-                                                                                                                Of the total number of subjects in clinical studies of LOKELMA, 58% were age 65 and over, while 25% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients.