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

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.