LOKELMATM Sodium Zirconium Cyclosilicate

SWIFT* K+ REDUCTION AFTER ONE HOUR.1,2
SUSTAINED K+ CONTROL FOR UP TO ONE YEAR
WHEN USED AS A MAINTENANCE THERAPY.†1
NOW IN YOUR HANDS.
New, highly-selective LOKELMA (sodium zirconium cyclosilicate)
is indicated for the treatment of hyperkalaemia in adult patients1

*In an emergency situation, standard of care should be used in line with local or national guidelines
Clinical trials with LOKELMA have not included exposure longer than one year

Product Information

Indication

LOKELMA is indicated for the treatment of hyperkalaemia in adult patients. In an emergency situation, standard of care should be used in line with local or national guidelines.1

About LOKELMA

  • For adult patients with hyperkalaemia, LOKELMA (sodium zirconium cyclosilicate) is highly selective and proven
    to significantly reduce potassium (K+) levels after 1 hour*1,2
  • 88% of patients achieved normokalaemia at 48 hours1
  • Once-daily maintenance dosing of LOKELMA sustains normokalaemia (3.5 - 5.0 mmol/L) for up to one year†1

*In an emergency situation, standard of care should be used in line with local or national guidelines.
Clinical trials with LOKELMA have not included exposure longer than 1 year.

Mechanism of Action

Novel, selective K+ capture3

LOKELMA captures K+ throughout the entire gastrointestinal (GI) tract and reduces the concentration of free K+ in the GI lumen, thereby increasing faecal K+ excretion to reduce serum levels of K+.1

Lattice structure uniquely designed to preferentially capture K+3

  • LOKELMA is a non-absorbed, non-polymer inorganic powder with a uniform micropore structure that preferentially captures K+ in exchange for Hydrogen and Sodium cations (Na+)1
  • LOKELMA is highly selective for K+ ions, even in the presence of other cations, such as Calcium (Ca+) and Magnesium (Mg2+), in vitro‡1
  • LOKELMA contains less than 8% Na+ by total weight. For example, one 5 g dose of LOKELMA contains 400 mg of Na+3 

      ‡In vitro data suggest LOKELMA works at different pHs found along the GI tract.

 

LOKELMA<sup>TM</sup> micropore structure that captures K+ to treat hyperkalaemia
LOKELMA<sup>TM</sup> micropore structure that captures K+ to treat hyperkalaemia

Adapted from Stavros F, et al. PLoS One. 2014;9(12):e114686.

  • Not systemically absorbed1
  • No effect on serum calcium or magnesium concentrations1
  • No effect on urinary Na+ excretion1

Prescribing LOKELMA

LOKELMA is a powder for oral suspension and is intended for oral use.1

To administer, mix LOKELMA with 3 tablespoons (a total of 45 mL) of water

  • The tasteless liquid should be drunk while still cloudy1
  • If the powder settles, the water should be stirred again1
  • It should be ensured that all of the content is taken1
Empty LOKELMA sachet into about 3 tablespoons of water
Empty LOKELMA sachet into about 3 tablespoons of water

LOKELMA can transiently increase gut pH by absorbing hydrogen ions, which can lead to changes in solubility and absorption kinetics for co-administered drugs with pH-dependent bioavailability. Therefore, LOKELMA should be administered at least 2 hours after or 2 hours before oral medications with gastric pH-dependent bioavailability.1

Drug–drug interactions are summarised in the section ‘drug interactions’ below, refer to prescribing information before use or SPC for further information.

Additional administration information:

  • Tasteless and odourless1,3
  • May be taken with many other medications1
  • May be taken with or without food1
  • No special conditions for storage1

Dosing

LOKELMA is a daily treatment option for hyperkalaemia, with a correction phase and maintenance phase.1

Correction phase

Recommended starting dose for adults and elderly is 10 g, administered orally, three times daily as a suspension in water, with or without food. LOKELMA should be administered at least 2 hours before or 2 hours after oral medications with gastric pH-dependent bioavailability. LOKELMA can be co-administered without spacing of dosing times with oral medications that do not exhibit pH-dependent bioavailability.1

*Illustrative only. The first dose of LOKELMA should be administered as soon as hyperkalaemia is identified when clinically indicated.
In an emergency situation, standard of care should be used in line with local or national guidelines.

Dose 10 g three times daily to initiate treatment for hyperkalaemia
Dose 10 g three times daily to initiate treatment for hyperkalaemia
  • Typically, normokalaemia is achieved within 24 to 48 hours1
  • If the patient is still hyperkalaemic after 48 hours of treatment the same regimen (10 g orally three times daily)
    can be continued for an additional 24 hours1
  • When normokalaemia is achieved, the maintenance regimen should be followed1
  • If normokalaemia is not achieved after 72 hours of treatment other treatment options should be considered1

Maintenance phase

Recommended starting dose for adults and elderly is 5 g once daily.1

Maintain normokalaemia1

Dosing in the maintenance phase to treat hyperkalaemia
Dosing in the maintenance phase to treat hyperkalaemia
  • Establish the minimal effective dose to prevent recurrence of hyperkalaemia1
  • Recommended starting dose of 5 g once daily, with possible titration up to 10 g once daily, or down to 5 g once every other day, as needed, to maintain normal K+ level1
  • No more than 10 g once daily should be used for maintenance therapy1

Additional dosing and monitoring information:

  • Monitor serum K+ levels regularly during treatment. Monitoring frequency will depend on factors such as other medications, progression of chronic kidney disease and dietary K+ intake. Discontinue and re-evaluate patient
    if severe hypokalaemia occurs1
  • Safety and efficacy has not been established in children and adolescents (<18 years of age)
  • Avoid during pregnancy1
  • No dose adjustment is required for renal/hepatic impairment1
  • No data is available for use in the dialysis population1
  • Clinical trials with LOKELMA have not included exposure longer than 1 year1

Warnings and Precautions

For a full list of warnings and precautions, please consult the LOKELMA (sodium zirconium cyclosilicate)
Summary of Product Characteristics, available at https://www.medicines.org.uk/emc.

The safety and efficacy of LOKELMA has been studied in more than 1,700 patients with hyperkalaemia (with 507 patients exposed for 1 year), including patients with chronic kidney disease, heart failure, diabetes and RAASi therapy.1

Contraindications

Hypersensitivity to the active substance.1

Warnings and precautions1

Serum K⁺ levels Monitor serum K⁺ levels when clinically indicated, including after changes are made to medicinal products that affect the serum K⁺ concentration (e.g. renin-angiotensin-aldosterone system [RAAS] inhibitors or diuretics) and after LOKELMA dose is titrated.
Hypokalaemia Hypokalaemia may be observed. To prevent moderate-to-severe hypokalaemia dose titration (maintenance posology) may be required. Discontinue and re-evaluate treatment in patients with severe hypokalaemia.
QT interval During correction phase, a lengthening of QT interval can be observed as the physiologic result of decline in serum K⁺ concentration.
Risk of interaction with X-rays LOKELMA may be opaque to X-rays – keep in mind if patient has abdominal X-ray.
Intestinal perforation Risk of intestinal perforation unknown. Special attention to be paid as intestinal perforation has been reported with polymers that act in the GI tract.
Patients on dialysis No experience with patients receiving dialysis treatment.
Severe hyperkalaemia Limited experience in patients with serum K⁺ concentrations greater than 6.5 mmol/L.
Pregnancy Preferable to avoid use during pregnancy. Can be used during breast-feeding.
Paediatrics Safety and efficacy have not been established in children and adolescents (<18 years).

 

 

Drug Interactions

No expected effects of other medicines on LOKELMA as it is not absorbed or metabolised by the body.1

LOKELMA can transiently increase gastric pH: 

  • As a result, LOKELMA can lead to changes in solubility where co-administered medicinal product has pH-dependent stability and therefore should be administered at least 2 hours before or 2 hours after oral medications with clinically meaningful gastric-pH-dependent bioavailability1
  • In a clinical drug–drug interaction study conducted in healthy subjects, co-administration of LOKELMA with amlodipine, clopidogrel, atorvastatin, furosemide, glipizide, warfarin, losartan or levothyroxine did not result in clinically meaningful drug–drug interactions. Consistent with co-administration of dabigatran with other gastric acid modifiers, dabigatran Cmax and AUC values were approximately 40% lower when co-administered with LOKELMA1
  • Examples of medicinal products that should be administered 2 hours before or after sodium zirconium cyclosilicate to avoid possible raised gastric pH drug interaction are: Azole antifungals (ketoconazole, itraconazole and posaconazole), anti-HIV drugs (atazanavir, nelfinavir, indinavir, ritonavir, saquinavir, raltegravir, ledipasvir and rilpivirine) and tyrosine kinase inhibitors (erlotinib, dasatinib and nilotinib)1
  • LOKELMA can be co-administered without spacing of dosing times with oral medications that do not exhibit pH-dependent bioavailability1

Cmax = Maximum serum concentration
AUC = Area under the curve

Adverse Events

In clinical trials, 4.1% of LOKELMA patients developed hypokalaemia, which resolved with dose adjustment or discontinuation of LOKELMA. In all clinical trials with varying durations of treatment oedema-related events (including fluid overload, fluid retention, generalised oedema, hypervolaemia, localised oedema, oedema, oedema peripheral and peripheral swelling) were reported by 5.7% of patients taking LOKELMA. In the single-armed 005 study phase with one year of treatment 15.1% of patients experienced oedema (9.7% peripheral oedema), with more events in those at higher risk of oedema (older patients; estimated glomerular filtration rate <45 ml/min per 1.73 m2; heart failure; K+ >5.5 mmol/L; and calcium channel blocker or diuretic use at baseline). Of these, 2.4% were attributed by investigators to LOKELMA but due to the lack of a control arm it is difficult to assess the additional contribution to oedema of LOKELMA.1,4

In 2 clinical studies with open label exposure of LOKELMA up to 1 year in 874 subjects, the following events were reported as related by investigators: GI events [constipation (2.9%), diarrhea (0.9%), abdominal pain/distension (0.5%), nausea (1.6%) and vomiting (0.5%)] and hypersensitivity reactions [rash (0.3%) and pruritus (0.1%)].1

These events were mild to moderate in nature, none were reported as serious and were generally resolved while the patient continued treatment.1

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AstraZeneca by visiting https://aereporting.astrazeneca.com or by calling 0800 783 0033.