Sodium zirconium cyclosilicate
Identification
- Summary
Sodium zirconium cyclosilicate is a potassium binder used to treat hyperkalemia.
- Brand Names
- Lokelma
- Generic Name
- Sodium zirconium cyclosilicate
- DrugBank Accession Number
- DB14048
- Background
Sodium zirconium cyclosilicate is approved as the trade product Lokelma developed by AstraZeneca - an insoluble, non-absorbed sodium zirconium silicate, formulated as a powder for oral suspension that acts as a highly selective potassium removing agent.2 It is administered orally and is odorless, tasteless, and stable at room temperature.2 Approval of the medication is supported by data from three double-blind, placebo-controlled trials and two open-label trials which showed that the onset of action was approximately 1.0 hour and the median time to achieving normal potassium levels in the blood was 2.2 hours, with 92% of patients achieving normal potassium levels within 48 hours following administration.2 The treatment effect was maintained for up to 12 months.2
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Sodium zirconium cyclosilicate (DB14048)
- Weight
- Average: 365.452
Monoisotopic: 363.77144 - Chemical Formula
- Na2O9Si3Zr
- Synonyms
- Sodium zirconium cyclosilicate
- Sodium zirconium silicate
- External IDs
- UXSI-9
- ZS
- ZS-9
Pharmacology
- Indication
Sodium zirconium cyclosilicate is a potassium binder indicated for the treatment of hyperkalemia in adult patients.3,4
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- Contraindications & Blackbox Warnings
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Sodium zirconium cyclosilicate is capable of reducing serum potassium concentrations as quickly as one hour after ingestion and normokalaemia can be achieved typically within 24 to 48 hours.3,4 Sodium zirconium cyclosilicate does not affect serum calcium or magnesium concentrations, or urinary sodium excretion.3,4 A close correlation is observed between starting serum potassium levels and effect size; patients with higher starting serum potassium levels have greater reductions in serum potassium.3,4 As a consequence of the resultant reduction in serum potassium concentration, there is a reduction in urinary potassium excretion as well.3,4 In a study of healthy subjects given sodium zirconium cyclosilicate 5 or 10 grams daily for four days, a dose-dependent reduction in serum potassium concentration and total urinary potassium excretion were accompanied by mean increases in fecal potassium excretion.3,4 No statistically significant changes in urinary sodium excretion were observed.3,4
Sodium zirconium cyclosilicate has also been observed to bind ammonium in vitro and in vivo, thereby removing ammonium and increasing serum bicarbonate levels.4 Patients treated with sodium zirconium cyclosilicate were documented as experiencing an increase of 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 in bicarbonate compared with a mean increase of 0.6 mmol/L for the patients receiving placebo.4 In an environment where other factors affecting renin and aldosterone were not controlled, sodium zirconium cyclosilicate demonstrated a dose-independent reduction in mean serum aldosterone levels (range of -30% to -31%) compared with the placebo group (+14%).4 No consistent effect on systolic and diastolic blood pressure has yet to be observed.4
Moreover, mean reductions in blood urea nitrogen (BUN) were observed in the 5 g (-1.1 mg/dL) and 10 g (-2.0 mg/dL) three times daily groups compared with small mean increases in the placebo (0.8 mg/dL) and low dose sodium zirconium cyclosilicate (0.3 mg/dL).4
- Mechanism of action
Hyperkalemia is a condition defined by elevated potassium levels in the blood, often caused by cardiovascular, renal, and metabolic diseases.1 Hyperkalemia occurs in 23 to 47% of patients with chronic kidney disease and/or chronic heart failure, and may lead to cardiac arrest and death.1
Sodium zirconium cyclosilicate is subsequently a non-absorbed, non-polymer inorganic powder with a uniform micropore structure that preferentially captures potassium in exchange for hydrogen and sodium cations.3,4 Sodium zirconium cyclosilicate is highly selective for potassium ions, even in the presence of other cations such as calcium and magnesium, in vitro.3,4 Sodium zirconium cyclosilicate captures potassium throughout the entire gastrointestinal (GI) tract and reduces the concentration of free potassium in the GI lumen, thereby lowering serum potassium levels and increasing fecal potassium excretion to resolve hyperkalemia.3,4
Target Actions Organism APotassium binderHumans - Absorption
Sodium zirconium cyclosilicate is an inorganic, insoluble compound that is not susceptible to enzymatic metabolism.4 Additionally, studies have shown it not to be systemically absorbed either.4 An in vivo mass balance study in rats showed that sodium zirconium cyclosilicate was recovered in the feces with no evidence of systemic absorption.4
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Sodium zirconium cyclosilicate is an inorganic, insoluble compound that is not susceptible to enzymatic metabolism.4 Additionally, studies have shown it not to be systemically absorbed either.4 An in vivo mass balance study in rats showed that sodium zirconium cyclosilicate was recovered in the feces with no evidence of systemic absorption.4 Due to these factors and its insolubility, no in vivo or in vitro studies have thus far been performed to examine its effect on cytochrome P450 (CYP450) enzymes or transporter activity.4
- Route of elimination
Sodium zirconium cyclosilicate is eliminated in the feces.4
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Overdose with sodium zirconium cyclosilicate could lead to hypokalemia.3,4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmprenavir Sodium zirconium cyclosilicate can cause a decrease in the absorption of Amprenavir resulting in a reduced serum concentration and potentially a decrease in efficacy. Asunaprevir Sodium zirconium cyclosilicate can cause a decrease in the absorption of Asunaprevir resulting in a reduced serum concentration and potentially a decrease in efficacy. Atazanavir Sodium zirconium cyclosilicate can cause a decrease in the absorption of Atazanavir resulting in a reduced serum concentration and potentially a decrease in efficacy. Bisacodyl The therapeutic efficacy of Bisacodyl can be decreased when used in combination with Sodium zirconium cyclosilicate. Bosutinib Sodium zirconium cyclosilicate can cause a decrease in the absorption of Bosutinib resulting in a reduced serum concentration and potentially a decrease in efficacy. Captopril Sodium zirconium cyclosilicate can cause a decrease in the absorption of Captopril resulting in a reduced serum concentration and potentially a decrease in efficacy. Cefditoren The serum concentration of Cefditoren can be decreased when it is combined with Sodium zirconium cyclosilicate. Cefuroxime The serum concentration of Cefuroxime can be decreased when it is combined with Sodium zirconium cyclosilicate. Cysteamine The bioavailability of Cysteamine can be decreased when combined with Sodium zirconium cyclosilicate. Dabigatran etexilate Sodium zirconium cyclosilicate can cause a decrease in the absorption of Dabigatran etexilate resulting in a reduced serum concentration and potentially a decrease in efficacy. 
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- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lokelma Powder, for suspension 5 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU 
Lokelma Powder, for suspension 10 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU Lokelma Powder, for suspension 5 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU Lokelma Powder, for suspension 10 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU Lokelma Powder, for suspension 5 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU Lokelma Powder, for suspension 10 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU Lokelma Powder, for suspension 10 g / sachet Oral Astra Zeneca 2019-10-17 Not applicable Canada 
Lokelma Powder, for suspension 10 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU Lokelma Powder, for suspension 10 g/10g Oral AstraZeneca Pharmaceuticals LP 2018-09-04 Not applicable US 
Lokelma Powder, for suspension 10 g Oral Astra Zeneca Ab 2020-12-16 Not applicable EU
Categories
- ATC Codes
- V03AE10 — Sodium zirconium cyclosilicate
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- D652ZWF066
- CAS number
- 17141-74-1
- InChI Key
- ARVUQMBOTBOHPL-UHFFFAOYSA-N
- InChI
- InChI=1S/2Na.O9Si3.Zr/c;;1-10(2)7-11(3,4)9-12(5,6)8-10;/q2*+1;-6;
- IUPAC Name
- disodium 1,3,5,2,4,6-trioxatrisilinane-2,2,4,4,6,6-hexakis(olate) zirconium
- SMILES
- [Na+].[Na+].[Zr].[O-][Si]1([O-])O[Si]([O-])([O-])O[Si]([O-])([O-])O1
References
- General References
- AstraZeneca: ZS-9 (sodium zirconium cyclosilicate) Phase III long-term safety and efficacy data presented at ASN Kidney Week 2017 [Link]
- AstraZeneca: Lokelma approved in the US for the treatment of adults with hyperkalaemia [Link]
- FDA Approved Drug Products: Lokelma (sodium zirconium cyclosilicate) for oral suspension [Link]
- EMA Sodium Zirconium Cyclosilicate Monograph [File]
- External Links
- KEGG Drug
- D10727
- 2047628
- Wikipedia
- Sodium_zirconium_cyclosilicate
- FDA label
- Download (374 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Acute Hyperkalemia / Oral Potassium Binders 1 4 Recruiting Treatment Heart Failure With Reduced Ejection Fraction (HFrEF) / Hyperkalemia 1 4 Recruiting Treatment Type 2 Diabetes Mellitus With Kidney Complications 1 3 Completed Supportive Care Hyperkalemia 4 3 Completed Treatment Hyperkalemia 2 3 Recruiting Treatment Chronic Kidney Disease (CKD) / Hyperkalemia / Metabolic Acidosis 1 3 Recruiting Treatment Hyperkalemia 4 2 Completed Treatment Hyperkalemia 1 2 Not Yet Recruiting Treatment Heart Failure / Hyperkalemia 1 2 Terminated Treatment Heart Failure 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Powder, for suspension Oral Powder, for suspension Oral 10 g/10g Powder, for suspension Oral 10 g Powder, for suspension Oral 10 g / sachet Powder, for suspension Oral 5 g/5g Powder, for suspension Oral 5 g Powder, for suspension Oral 5 g / sachet Suspension Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9592253 No 2017-03-14 2035-10-14 US US8808750 No 2014-08-19 2032-02-10 US US9844567 No 2017-12-19 2032-02-10 US US9861658 No 2018-01-09 2032-02-10 US US6332985 No 2001-12-25 2019-03-29 US US8877255 No 2014-11-04 2033-10-22 US US8802152 No 2014-08-12 2032-04-19 US US9913860 No 2018-03-13 2033-10-22 US US10335432 No 2019-07-02 2032-02-10 US US10300087 No 2019-05-28 2035-10-14 US US10398730 No 2019-09-03 2032-02-10 US US10413569 No 2019-09-17 2032-02-10 US US10695365 No 2013-10-22 2033-10-22 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source logP -3.8 ChemAxon pKa (Strongest Acidic) 6.97 ChemAxon pKa (Strongest Basic) -4.4 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 9 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 166.05 Å2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 12.71 m3·mol-1 ChemAxon Polarizability 12.77 Å3 ChemAxon Number of Rings 1 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
Drug created on June 05, 2018 16:19 / Updated on August 04, 2021 18:23